CINXE.COM

<!DOCTYPE html> <html class="client-nojs vector-feature-language-in-header-enabled vector-feature-language-in-main-page-header-disabled vector-feature-sticky-header-disabled vector-feature-page-tools-pinned-disabled vector-feature-toc-pinned-clientpref-1 vector-feature-main-menu-pinned-disabled vector-feature-limited-width-clientpref-1 vector-feature-limited-width-content-enabled vector-feature-custom-font-size-clientpref-1 vector-feature-appearance-pinned-clientpref-1 vector-feature-night-mode-enabled skin-theme-clientpref-day vector-toc-available" lang="en" dir="ltr"> <head> <meta charset="UTF-8"> <title>Genome instability - Wikipedia</title> <script>(function(){var className="client-js vector-feature-language-in-header-enabled vector-feature-language-in-main-page-header-disabled vector-feature-sticky-header-disabled vector-feature-page-tools-pinned-disabled vector-feature-toc-pinned-clientpref-1 vector-feature-main-menu-pinned-disabled vector-feature-limited-width-clientpref-1 vector-feature-limited-width-content-enabled vector-feature-custom-font-size-clientpref-1 vector-feature-appearance-pinned-clientpref-1 vector-feature-night-mode-enabled skin-theme-clientpref-day vector-toc-available";var cookie=document.cookie.match(/(?:^|; )enwikimwclientpreferences=([^;]+)/);if(cookie){cookie[1].split('%2C').forEach(function(pref){className=className.replace(new RegExp('(^| )'+pref.replace(/-clientpref-\w+$|[^\w-]+/g,'')+'-clientpref-\\w+( |$)'),'$1'+pref+'$2');});}document.documentElement.className=className;}());RLCONF={"wgBreakFrames":false,"wgSeparatorTransformTable":["",""],"wgDigitTransformTable":["",""],"wgDefaultDateFormat":"dmy", "wgMonthNames":["","January","February","March","April","May","June","July","August","September","October","November","December"],"wgRequestId":"97ab7285-3aa0-4aac-b474-2a436c24c6c5","wgCanonicalNamespace":"","wgCanonicalSpecialPageName":false,"wgNamespaceNumber":0,"wgPageName":"Genome_instability","wgTitle":"Genome instability","wgCurRevisionId":1238604012,"wgRevisionId":1238604012,"wgArticleId":32706791,"wgIsArticle":true,"wgIsRedirect":false,"wgAction":"view","wgUserName":null,"wgUserGroups":["*"],"wgCategories":["Articles with short description","Short description matches Wikidata","All articles with unsourced statements","Articles with unsourced statements from February 2024","Articles with unsourced statements from December 2019","Chromosomes","Cancer","Mutation"],"wgPageViewLanguage":"en","wgPageContentLanguage":"en","wgPageContentModel":"wikitext","wgRelevantPageName":"Genome_instability","wgRelevantArticleId":32706791,"wgIsProbablyEditable":true, "wgRelevantPageIsProbablyEditable":true,"wgRestrictionEdit":[],"wgRestrictionMove":[],"wgNoticeProject":"wikipedia","wgCiteReferencePreviewsActive":false,"wgFlaggedRevsParams":{"tags":{"status":{"levels":1}}},"wgMediaViewerOnClick":true,"wgMediaViewerEnabledByDefault":true,"wgPopupsFlags":0,"wgVisualEditor":{"pageLanguageCode":"en","pageLanguageDir":"ltr","pageVariantFallbacks":"en"},"wgMFDisplayWikibaseDescriptions":{"search":true,"watchlist":true,"tagline":false,"nearby":true},"wgWMESchemaEditAttemptStepOversample":false,"wgWMEPageLength":40000,"wgRelatedArticlesCompat":[],"wgCentralAuthMobileDomain":false,"wgEditSubmitButtonLabelPublish":true,"wgULSPosition":"interlanguage","wgULSisCompactLinksEnabled":false,"wgVector2022LanguageInHeader":true,"wgULSisLanguageSelectorEmpty":false,"wgWikibaseItemId":"Q2892636","wgCheckUserClientHintsHeadersJsApi":["brands","architecture","bitness","fullVersionList","mobile","model","platform","platformVersion"],"GEHomepageSuggestedEditsEnableTopics": true,"wgGETopicsMatchModeEnabled":false,"wgGEStructuredTaskRejectionReasonTextInputEnabled":false,"wgGELevelingUpEnabledForUser":false};RLSTATE={"ext.globalCssJs.user.styles":"ready","site.styles":"ready","user.styles":"ready","ext.globalCssJs.user":"ready","user":"ready","user.options":"loading","ext.cite.styles":"ready","skins.vector.search.codex.styles":"ready","skins.vector.styles":"ready","skins.vector.icons":"ready","ext.wikimediamessages.styles":"ready","ext.visualEditor.desktopArticleTarget.noscript":"ready","ext.uls.interlanguage":"ready","wikibase.client.init":"ready","ext.wikimediaBadges":"ready"};RLPAGEMODULES=["ext.cite.ux-enhancements","site","mediawiki.page.ready","mediawiki.toc","skins.vector.js","ext.centralNotice.geoIP","ext.centralNotice.startUp","ext.gadget.ReferenceTooltips","ext.gadget.switcher","ext.urlShortener.toolbar","ext.centralauth.centralautologin","mmv.bootstrap","ext.popups","ext.visualEditor.desktopArticleTarget.init","ext.visualEditor.targetLoader", "ext.echo.centralauth","ext.eventLogging","ext.wikimediaEvents","ext.navigationTiming","ext.uls.interface","ext.cx.eventlogging.campaigns","ext.cx.uls.quick.actions","wikibase.client.vector-2022","ext.checkUser.clientHints","ext.growthExperiments.SuggestedEditSession","wikibase.sidebar.tracking"];</script> <script>(RLQ=window.RLQ||[]).push(function(){mw.loader.impl(function(){return["user.options@12s5i",function($,jQuery,require,module){mw.user.tokens.set({"patrolToken":"+\\","watchToken":"+\\","csrfToken":"+\\"}); }];});});</script> <link rel="stylesheet" href="/w/load.php?lang=en&modules=ext.cite.styles%7Cext.uls.interlanguage%7Cext.visualEditor.desktopArticleTarget.noscript%7Cext.wikimediaBadges%7Cext.wikimediamessages.styles%7Cskins.vector.icons%2Cstyles%7Cskins.vector.search.codex.styles%7Cwikibase.client.init&only=styles&skin=vector-2022"> <script async="" src="/w/load.php?lang=en&modules=startup&only=scripts&raw=1&skin=vector-2022"></script> <meta name="ResourceLoaderDynamicStyles" content=""> <link rel="stylesheet" href="/w/load.php?lang=en&modules=site.styles&only=styles&skin=vector-2022"> <meta name="generator" content="MediaWiki 1.44.0-wmf.4"> <meta name="referrer" content="origin"> <meta name="referrer" content="origin-when-cross-origin"> <meta name="robots" content="max-image-preview:standard"> <meta name="format-detection" content="telephone=no"> <meta name="viewport" content="width=1120"> <meta property="og:title" content="Genome instability - Wikipedia"> <meta property="og:type" content="website"> <link rel="preconnect" href="//upload.wikimedia.org"> <link rel="alternate" media="only screen and (max-width: 640px)" href="//en.m.wikipedia.org/wiki/Genome_instability"> <link rel="alternate" type="application/x-wiki" title="Edit this page" href="/w/index.php?title=Genome_instability&action=edit"> <link rel="apple-touch-icon" href="/static/apple-touch/wikipedia.png"> <link rel="icon" href="/static/favicon/wikipedia.ico"> <link rel="search" type="application/opensearchdescription+xml" href="/w/rest.php/v1/search" title="Wikipedia (en)"> <link rel="EditURI" type="application/rsd+xml" href="//en.wikipedia.org/w/api.php?action=rsd"> <link rel="canonical" href="https://en.wikipedia.org/wiki/Genome_instability"> <link rel="license" href="https://creativecommons.org/licenses/by-sa/4.0/deed.en"> <link rel="alternate" type="application/atom+xml" title="Wikipedia Atom feed" href="/w/index.php?title=Special:RecentChanges&feed=atom"> <link rel="dns-prefetch" href="//meta.wikimedia.org" /> <link rel="dns-prefetch" href="//login.wikimedia.org"> </head> <body class="skin--responsive skin-vector skin-vector-search-vue mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-0 ns-subject mw-editable page-Genome_instability rootpage-Genome_instability skin-vector-2022 action-view"><a class="mw-jump-link" href="#bodyContent">Jump to content</a> <div class="vector-header-container"> <header class="vector-header mw-header"> <div class="vector-header-start"> <nav class="vector-main-menu-landmark" aria-label="Site"> <div id="vector-main-menu-dropdown" class="vector-dropdown vector-main-menu-dropdown vector-button-flush-left vector-button-flush-right" > <input type="checkbox" id="vector-main-menu-dropdown-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-main-menu-dropdown" class="vector-dropdown-checkbox " aria-label="Main menu" > <label id="vector-main-menu-dropdown-label" for="vector-main-menu-dropdown-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only " aria-hidden="true" ><span class="vector-icon mw-ui-icon-menu mw-ui-icon-wikimedia-menu"></span> <span class="vector-dropdown-label-text">Main menu</span> </label> <div class="vector-dropdown-content"> <div id="vector-main-menu-unpinned-container" class="vector-unpinned-container"> <div id="vector-main-menu" class="vector-main-menu vector-pinnable-element"> <div class="vector-pinnable-header vector-main-menu-pinnable-header vector-pinnable-header-unpinned" data-feature-name="main-menu-pinned" data-pinnable-element-id="vector-main-menu" data-pinned-container-id="vector-main-menu-pinned-container" data-unpinned-container-id="vector-main-menu-unpinned-container" > <div class="vector-pinnable-header-label">Main menu</div> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-pin-button" data-event-name="pinnable-header.vector-main-menu.pin">move to sidebar</button> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-unpin-button" data-event-name="pinnable-header.vector-main-menu.unpin">hide</button> </div> <div id="p-navigation" class="vector-menu mw-portlet mw-portlet-navigation" > <div class="vector-menu-heading"> Navigation </div> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="n-mainpage-description" class="mw-list-item"><a href="/wiki/Main_Page" title="Visit the main page [z]" accesskey="z"><span>Main page</span></a></li><li id="n-contents" class="mw-list-item"><a href="/wiki/Wikipedia:Contents" title="Guides to browsing Wikipedia"><span>Contents</span></a></li><li id="n-currentevents" class="mw-list-item"><a href="/wiki/Portal:Current_events" title="Articles related to current events"><span>Current events</span></a></li><li id="n-randompage" class="mw-list-item"><a href="/wiki/Special:Random" title="Visit a randomly selected article [x]" accesskey="x"><span>Random article</span></a></li><li id="n-aboutsite" class="mw-list-item"><a href="/wiki/Wikipedia:About" title="Learn about Wikipedia and how it works"><span>About Wikipedia</span></a></li><li id="n-contactpage" class="mw-list-item"><a href="//en.wikipedia.org/wiki/Wikipedia:Contact_us" title="How to contact Wikipedia"><span>Contact us</span></a></li> </ul> </div> </div> <div id="p-interaction" class="vector-menu mw-portlet mw-portlet-interaction" > <div class="vector-menu-heading"> Contribute </div> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="n-help" class="mw-list-item"><a href="/wiki/Help:Contents" title="Guidance on how to use and edit Wikipedia"><span>Help</span></a></li><li id="n-introduction" class="mw-list-item"><a href="/wiki/Help:Introduction" title="Learn how to edit Wikipedia"><span>Learn to edit</span></a></li><li id="n-portal" class="mw-list-item"><a href="/wiki/Wikipedia:Community_portal" title="The hub for editors"><span>Community portal</span></a></li><li id="n-recentchanges" class="mw-list-item"><a href="/wiki/Special:RecentChanges" title="A list of recent changes to Wikipedia [r]" accesskey="r"><span>Recent changes</span></a></li><li id="n-upload" class="mw-list-item"><a href="/wiki/Wikipedia:File_upload_wizard" title="Add images or other media for use on Wikipedia"><span>Upload file</span></a></li> </ul> </div> </div> </div> </div> </div> </div> </nav> <a href="/wiki/Main_Page" class="mw-logo"> <img class="mw-logo-icon" src="/static/images/icons/wikipedia.png" alt="" aria-hidden="true" height="50" width="50"> <span class="mw-logo-container skin-invert"> <img class="mw-logo-wordmark" alt="Wikipedia" src="/static/images/mobile/copyright/wikipedia-wordmark-en.svg" style="width: 7.5em; height: 1.125em;"> <img class="mw-logo-tagline" alt="The Free Encyclopedia" src="/static/images/mobile/copyright/wikipedia-tagline-en.svg" width="117" height="13" style="width: 7.3125em; height: 0.8125em;"> </span> </a> </div> <div class="vector-header-end"> <div id="p-search" role="search" class="vector-search-box-vue vector-search-box-collapses vector-search-box-show-thumbnail vector-search-box-auto-expand-width vector-search-box"> <a href="/wiki/Special:Search" class="cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only search-toggle" title="Search Wikipedia [f]" accesskey="f"><span class="vector-icon mw-ui-icon-search mw-ui-icon-wikimedia-search"></span> <span>Search</span> </a> <div class="vector-typeahead-search-container"> <div class="cdx-typeahead-search cdx-typeahead-search--show-thumbnail cdx-typeahead-search--auto-expand-width"> <form action="/w/index.php" id="searchform" class="cdx-search-input cdx-search-input--has-end-button"> <div id="simpleSearch" class="cdx-search-input__input-wrapper" data-search-loc="header-moved"> <div class="cdx-text-input cdx-text-input--has-start-icon"> <input class="cdx-text-input__input" type="search" name="search" placeholder="Search Wikipedia" aria-label="Search Wikipedia" autocapitalize="sentences" title="Search Wikipedia [f]" accesskey="f" id="searchInput" > <span class="cdx-text-input__icon cdx-text-input__start-icon"></span> </div> <input type="hidden" name="title" value="Special:Search"> </div> <button class="cdx-button cdx-search-input__end-button">Search</button> </form> </div> </div> </div> <nav class="vector-user-links vector-user-links-wide" aria-label="Personal tools"> <div class="vector-user-links-main"> <div id="p-vector-user-menu-preferences" class="vector-menu mw-portlet emptyPortlet" > <div class="vector-menu-content"> <ul class="vector-menu-content-list"> </ul> </div> </div> <div id="p-vector-user-menu-userpage" class="vector-menu mw-portlet emptyPortlet" > <div class="vector-menu-content"> <ul class="vector-menu-content-list"> </ul> </div> </div> <nav class="vector-appearance-landmark" aria-label="Appearance"> <div id="vector-appearance-dropdown" class="vector-dropdown " title="Change the appearance of the page's font size, width, and color" > <input type="checkbox" id="vector-appearance-dropdown-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-appearance-dropdown" class="vector-dropdown-checkbox " aria-label="Appearance" > <label id="vector-appearance-dropdown-label" for="vector-appearance-dropdown-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only " aria-hidden="true" ><span class="vector-icon mw-ui-icon-appearance mw-ui-icon-wikimedia-appearance"></span> <span class="vector-dropdown-label-text">Appearance</span> </label> <div class="vector-dropdown-content"> <div id="vector-appearance-unpinned-container" class="vector-unpinned-container"> </div> </div> </div> </nav> <div id="p-vector-user-menu-notifications" class="vector-menu mw-portlet emptyPortlet" > <div class="vector-menu-content"> <ul class="vector-menu-content-list"> </ul> </div> </div> <div id="p-vector-user-menu-overflow" class="vector-menu mw-portlet" > <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="pt-sitesupport-2" class="user-links-collapsible-item mw-list-item user-links-collapsible-item"><a data-mw="interface" href="https://donate.wikimedia.org/wiki/Special:FundraiserRedirector?utm_source=donate&utm_medium=sidebar&utm_campaign=C13_en.wikipedia.org&uselang=en" class=""><span>Donate</span></a> </li> <li id="pt-createaccount-2" class="user-links-collapsible-item mw-list-item user-links-collapsible-item"><a data-mw="interface" href="/w/index.php?title=Special:CreateAccount&returnto=Genome+instability" title="You are encouraged to create an account and log in; however, it is not mandatory" class=""><span>Create account</span></a> </li> <li id="pt-login-2" class="user-links-collapsible-item mw-list-item user-links-collapsible-item"><a data-mw="interface" href="/w/index.php?title=Special:UserLogin&returnto=Genome+instability" title="You're encouraged to log in; however, it's not mandatory. [o]" accesskey="o" class=""><span>Log in</span></a> </li> </ul> </div> </div> </div> <div id="vector-user-links-dropdown" class="vector-dropdown vector-user-menu vector-button-flush-right vector-user-menu-logged-out" title="Log in and more options" > <input type="checkbox" id="vector-user-links-dropdown-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-user-links-dropdown" class="vector-dropdown-checkbox " aria-label="Personal tools" > <label id="vector-user-links-dropdown-label" for="vector-user-links-dropdown-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only " aria-hidden="true" ><span class="vector-icon mw-ui-icon-ellipsis mw-ui-icon-wikimedia-ellipsis"></span> <span class="vector-dropdown-label-text">Personal tools</span> </label> <div class="vector-dropdown-content"> <div id="p-personal" class="vector-menu mw-portlet mw-portlet-personal user-links-collapsible-item" title="User menu" > <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="pt-sitesupport" class="user-links-collapsible-item mw-list-item"><a href="https://donate.wikimedia.org/wiki/Special:FundraiserRedirector?utm_source=donate&utm_medium=sidebar&utm_campaign=C13_en.wikipedia.org&uselang=en"><span>Donate</span></a></li><li id="pt-createaccount" class="user-links-collapsible-item mw-list-item"><a href="/w/index.php?title=Special:CreateAccount&returnto=Genome+instability" title="You are encouraged to create an account and log in; however, it is not mandatory"><span class="vector-icon mw-ui-icon-userAdd mw-ui-icon-wikimedia-userAdd"></span> <span>Create account</span></a></li><li id="pt-login" class="user-links-collapsible-item mw-list-item"><a href="/w/index.php?title=Special:UserLogin&returnto=Genome+instability" title="You're encouraged to log in; however, it's not mandatory. [o]" accesskey="o"><span class="vector-icon mw-ui-icon-logIn mw-ui-icon-wikimedia-logIn"></span> <span>Log in</span></a></li> </ul> </div> </div> <div id="p-user-menu-anon-editor" class="vector-menu mw-portlet mw-portlet-user-menu-anon-editor" > <div class="vector-menu-heading"> Pages for logged out editors <a href="/wiki/Help:Introduction" aria-label="Learn more about editing"><span>learn more</span></a> </div> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="pt-anoncontribs" class="mw-list-item"><a href="/wiki/Special:MyContributions" title="A list of edits made from this IP address [y]" accesskey="y"><span>Contributions</span></a></li><li id="pt-anontalk" class="mw-list-item"><a href="/wiki/Special:MyTalk" title="Discussion about edits from this IP address [n]" accesskey="n"><span>Talk</span></a></li> </ul> </div> </div> </div> </div> </nav> </div> </header> </div> <div class="mw-page-container"> <div class="mw-page-container-inner"> <div class="vector-sitenotice-container"> <div id="siteNotice"></div> </div> <div class="vector-column-start"> <div class="vector-main-menu-container"> <div id="mw-navigation"> <nav id="mw-panel" class="vector-main-menu-landmark" aria-label="Site"> <div id="vector-main-menu-pinned-container" class="vector-pinned-container"> </div> </nav> </div> </div> <div class="vector-sticky-pinned-container"> <nav id="mw-panel-toc" aria-label="Contents" data-event-name="ui.sidebar-toc" class="mw-table-of-contents-container vector-toc-landmark"> <div id="vector-toc-pinned-container" class="vector-pinned-container"> <div id="vector-toc" class="vector-toc vector-pinnable-element"> <div class="vector-pinnable-header vector-toc-pinnable-header vector-pinnable-header-pinned" data-feature-name="toc-pinned" data-pinnable-element-id="vector-toc" > <h2 class="vector-pinnable-header-label">Contents</h2> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-pin-button" data-event-name="pinnable-header.vector-toc.pin">move to sidebar</button> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-unpin-button" data-event-name="pinnable-header.vector-toc.unpin">hide</button> </div> <ul class="vector-toc-contents" id="mw-panel-toc-list"> <li id="toc-mw-content-text" class="vector-toc-list-item vector-toc-level-1"> <a href="#" class="vector-toc-link"> <div class="vector-toc-text">(Top)</div> </a> </li> <li id="toc-Usual_genome_situation" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Usual_genome_situation"> <div class="vector-toc-text"> <span class="vector-toc-numb">1</span> <span>Usual genome situation</span> </div> </a> <ul id="toc-Usual_genome_situation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Causes_of_genome_instability" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Causes_of_genome_instability"> <div class="vector-toc-text"> <span class="vector-toc-numb">2</span> <span>Causes of genome instability</span> </div> </a> <button aria-controls="toc-Causes_of_genome_instability-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Causes of genome instability subsection</span> </button> <ul id="toc-Causes_of_genome_instability-sublist" class="vector-toc-list"> <li id="toc-DNA_Replication_Defects" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#DNA_Replication_Defects"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.1</span> <span>DNA Replication Defects</span> </div> </a> <ul id="toc-DNA_Replication_Defects-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Fragile_Sites" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Fragile_Sites"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.2</span> <span>Fragile Sites</span> </div> </a> <ul id="toc-Fragile_Sites-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Transcription-associated_instability" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Transcription-associated_instability"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.3</span> <span>Transcription-associated instability</span> </div> </a> <ul id="toc-Transcription-associated_instability-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Increase_Genetic_Variability" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Increase_Genetic_Variability"> <div class="vector-toc-text"> <span class="vector-toc-numb">2.4</span> <span>Increase Genetic Variability</span> </div> </a> <ul id="toc-Increase_Genetic_Variability-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-In_neuronal_and_neuromuscular_disease" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#In_neuronal_and_neuromuscular_disease"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>In neuronal and neuromuscular disease</span> </div> </a> <ul id="toc-In_neuronal_and_neuromuscular_disease-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-In_cancer" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#In_cancer"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>In cancer</span> </div> </a> <button aria-controls="toc-In_cancer-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle In cancer subsection</span> </button> <ul id="toc-In_cancer-sublist" class="vector-toc-list"> <li id="toc-Low_frequency_of_mutations_without_cancer" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Low_frequency_of_mutations_without_cancer"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.1</span> <span>Low frequency of mutations without cancer</span> </div> </a> <ul id="toc-Low_frequency_of_mutations_without_cancer-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Cause_of_mutations_in_cancer" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Cause_of_mutations_in_cancer"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.2</span> <span>Cause of mutations in cancer</span> </div> </a> <ul id="toc-Cause_of_mutations_in_cancer-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Very_frequent_mutations_in_cancer" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Very_frequent_mutations_in_cancer"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.3</span> <span>Very frequent mutations in cancer</span> </div> </a> <ul id="toc-Very_frequent_mutations_in_cancer-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Cause_of_high_frequency_of_mutations_in_cancer" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Cause_of_high_frequency_of_mutations_in_cancer"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.4</span> <span>Cause of high frequency of mutations in cancer</span> </div> </a> <ul id="toc-Cause_of_high_frequency_of_mutations_in_cancer-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-DNA_repair_deficiency_in_cancer" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#DNA_repair_deficiency_in_cancer"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.5</span> <span>DNA repair deficiency in cancer</span> </div> </a> <ul id="toc-DNA_repair_deficiency_in_cancer-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Lymphomas_as_a_consequence_of_genome_instability" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Lymphomas_as_a_consequence_of_genome_instability"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.6</span> <span>Lymphomas as a consequence of genome instability</span> </div> </a> <ul id="toc-Lymphomas_as_a_consequence_of_genome_instability-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-In_aging" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#In_aging"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>In aging</span> </div> </a> <ul id="toc-In_aging-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">6</span> <span>References</span> </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" class="vector-dropdown vector-page-titlebar-toc vector-button-flush-left" > <input type="checkbox" id="vector-page-titlebar-toc-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-page-titlebar-toc" class="vector-dropdown-checkbox " aria-label="Toggle the table of contents" > <label id="vector-page-titlebar-toc-label" for="vector-page-titlebar-toc-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only " aria-hidden="true" ><span class="vector-icon mw-ui-icon-listBullet mw-ui-icon-wikimedia-listBullet"></span> <span class="vector-dropdown-label-text">Toggle the table of contents</span> </label> <div class="vector-dropdown-content"> <div id="vector-page-titlebar-toc-unpinned-container" class="vector-unpinned-container"> </div> </div> </div> </nav> <h1 id="firstHeading" class="firstHeading mw-first-heading"><span class="mw-page-title-main">Genome instability</span></h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. Available in 6 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-6" aria-hidden="true" ><span class="vector-icon mw-ui-icon-language-progressive mw-ui-icon-wikimedia-language-progressive"></span> <span class="vector-dropdown-label-text">6 languages</span> </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D8%B9%D8%AF%D9%85_%D8%A7%D8%B3%D8%AA%D9%82%D8%B1%D8%A7%D8%B1_%D8%A7%D9%84%D8%AC%D9%8A%D9%86%D9%88%D9%85" title="عدم استقرار الجينوم – Arabic" lang="ar" hreflang="ar" data-title="عدم استقرار الجينوم" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Inestabilidad_gen%C3%B3mica" title="Inestabilidad genómica – Spanish" lang="es" hreflang="es" data-title="Inestabilidad genómica" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/Inestabilidade_xen%C3%B3mica" title="Inestabilidade xenómica – Galician" lang="gl" hreflang="gl" data-title="Inestabilidade xenómica" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target"><span>Galego</span></a></li><li class="interlanguage-link interwiki-he mw-list-item"><a href="https://he.wikipedia.org/wiki/%D7%90%D7%99-%D7%99%D7%A6%D7%99%D7%91%D7%95%D7%AA_%D7%94%D7%92%D7%A0%D7%95%D7%9D" title="אי-יציבות הגנום – Hebrew" lang="he" hreflang="he" data-title="אי-יציבות הגנום" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target"><span>עברית</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E3%82%B2%E3%83%8E%E3%83%A0%E4%B8%8D%E5%AE%89%E5%AE%9A%E6%80%A7" title="ゲノム不安定性 – Japanese" lang="ja" hreflang="ja" data-title="ゲノム不安定性" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%93%D0%B5%D0%BD%D0%BE%D0%BC%D0%BD%D0%B0%D1%8F_%D0%BD%D0%B5%D1%81%D1%82%D0%B0%D0%B1%D0%B8%D0%BB%D1%8C%D0%BD%D0%BE%D1%81%D1%82%D1%8C" title="Геномная нестабильность – Russian" lang="ru" hreflang="ru" data-title="Геномная нестабильность" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li> </ul> <div class="after-portlet after-portlet-lang"><span class="wb-langlinks-edit wb-langlinks-link"><a href="https://www.wikidata.org/wiki/Special:EntityPage/Q2892636#sitelinks-wikipedia" title="Edit interlanguage links" class="wbc-editpage">Edit links</a></span></div> </div> </div> </div> </header> <div class="vector-page-toolbar"> <div class="vector-page-toolbar-container"> <div id="left-navigation"> <nav aria-label="Namespaces"> <div id="p-associated-pages" class="vector-menu vector-menu-tabs mw-portlet mw-portlet-associated-pages" > <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="ca-nstab-main" class="selected vector-tab-noicon mw-list-item"><a href="/wiki/Genome_instability" title="View the content page [c]" accesskey="c"><span>Article</span></a></li><li id="ca-talk" class="vector-tab-noicon mw-list-item"><a href="/wiki/Talk:Genome_instability" rel="discussion" title="Discuss improvements to the content page [t]" accesskey="t"><span>Talk</span></a></li> </ul> </div> </div> <div id="vector-variants-dropdown" class="vector-dropdown emptyPortlet" > <input type="checkbox" id="vector-variants-dropdown-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-variants-dropdown" class="vector-dropdown-checkbox " aria-label="Change language variant" > <label id="vector-variants-dropdown-label" for="vector-variants-dropdown-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet" aria-hidden="true" ><span class="vector-dropdown-label-text">English</span> </label> <div class="vector-dropdown-content"> <div id="p-variants" class="vector-menu mw-portlet mw-portlet-variants emptyPortlet" > <div class="vector-menu-content"> <ul class="vector-menu-content-list"> </ul> </div> </div> </div> </div> </nav> </div> <div id="right-navigation" class="vector-collapsible"> <nav aria-label="Views"> <div id="p-views" class="vector-menu vector-menu-tabs mw-portlet mw-portlet-views" > <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="ca-view" class="selected vector-tab-noicon mw-list-item"><a href="/wiki/Genome_instability"><span>Read</span></a></li><li id="ca-edit" class="vector-tab-noicon mw-list-item"><a href="/w/index.php?title=Genome_instability&action=edit" title="Edit this page [e]" accesskey="e"><span>Edit</span></a></li><li id="ca-history" class="vector-tab-noicon mw-list-item"><a href="/w/index.php?title=Genome_instability&action=history" title="Past revisions of this page [h]" accesskey="h"><span>View history</span></a></li> </ul> </div> </div> </nav> <nav class="vector-page-tools-landmark" aria-label="Page tools"> <div id="vector-page-tools-dropdown" class="vector-dropdown vector-page-tools-dropdown" > <input type="checkbox" id="vector-page-tools-dropdown-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-page-tools-dropdown" class="vector-dropdown-checkbox " aria-label="Tools" > <label id="vector-page-tools-dropdown-label" for="vector-page-tools-dropdown-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet" aria-hidden="true" ><span class="vector-dropdown-label-text">Tools</span> </label> <div class="vector-dropdown-content"> <div id="vector-page-tools-unpinned-container" class="vector-unpinned-container"> <div id="vector-page-tools" class="vector-page-tools vector-pinnable-element"> <div class="vector-pinnable-header vector-page-tools-pinnable-header vector-pinnable-header-unpinned" data-feature-name="page-tools-pinned" data-pinnable-element-id="vector-page-tools" data-pinned-container-id="vector-page-tools-pinned-container" data-unpinned-container-id="vector-page-tools-unpinned-container" > <div class="vector-pinnable-header-label">Tools</div> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-pin-button" data-event-name="pinnable-header.vector-page-tools.pin">move to sidebar</button> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-unpin-button" data-event-name="pinnable-header.vector-page-tools.unpin">hide</button> </div> <div id="p-cactions" class="vector-menu mw-portlet mw-portlet-cactions emptyPortlet vector-has-collapsible-items" title="More options" > <div class="vector-menu-heading"> Actions </div> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="ca-more-view" class="selected vector-more-collapsible-item mw-list-item"><a href="/wiki/Genome_instability"><span>Read</span></a></li><li id="ca-more-edit" class="vector-more-collapsible-item mw-list-item"><a href="/w/index.php?title=Genome_instability&action=edit" title="Edit this page [e]" accesskey="e"><span>Edit</span></a></li><li id="ca-more-history" class="vector-more-collapsible-item mw-list-item"><a href="/w/index.php?title=Genome_instability&action=history"><span>View history</span></a></li> </ul> </div> </div> <div id="p-tb" class="vector-menu mw-portlet mw-portlet-tb" > <div class="vector-menu-heading"> General </div> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="t-whatlinkshere" class="mw-list-item"><a href="/wiki/Special:WhatLinksHere/Genome_instability" title="List of all English Wikipedia pages containing links to this page [j]" accesskey="j"><span>What links here</span></a></li><li id="t-recentchangeslinked" class="mw-list-item"><a href="/wiki/Special:RecentChangesLinked/Genome_instability" rel="nofollow" title="Recent changes in pages linked from this page [k]" accesskey="k"><span>Related changes</span></a></li><li id="t-upload" class="mw-list-item"><a href="/wiki/Wikipedia:File_Upload_Wizard" title="Upload files [u]" accesskey="u"><span>Upload file</span></a></li><li id="t-specialpages" class="mw-list-item"><a href="/wiki/Special:SpecialPages" title="A list of all special pages [q]" accesskey="q"><span>Special pages</span></a></li><li id="t-permalink" class="mw-list-item"><a href="/w/index.php?title=Genome_instability&oldid=1238604012" title="Permanent link to this revision of this page"><span>Permanent link</span></a></li><li id="t-info" class="mw-list-item"><a href="/w/index.php?title=Genome_instability&action=info" title="More information about this page"><span>Page information</span></a></li><li id="t-cite" class="mw-list-item"><a href="/w/index.php?title=Special:CiteThisPage&page=Genome_instability&id=1238604012&wpFormIdentifier=titleform" title="Information on how to cite this page"><span>Cite this page</span></a></li><li id="t-urlshortener" class="mw-list-item"><a href="/w/index.php?title=Special:UrlShortener&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FGenome_instability"><span>Get shortened URL</span></a></li><li id="t-urlshortener-qrcode" class="mw-list-item"><a href="/w/index.php?title=Special:QrCode&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FGenome_instability"><span>Download QR code</span></a></li> </ul> </div> </div> <div id="p-coll-print_export" class="vector-menu mw-portlet mw-portlet-coll-print_export" > <div class="vector-menu-heading"> Print/export </div> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="coll-download-as-rl" class="mw-list-item"><a href="/w/index.php?title=Special:DownloadAsPdf&page=Genome_instability&action=show-download-screen" title="Download this page as a PDF file"><span>Download as PDF</span></a></li><li id="t-print" class="mw-list-item"><a href="/w/index.php?title=Genome_instability&printable=yes" title="Printable version of this page [p]" accesskey="p"><span>Printable version</span></a></li> </ul> </div> </div> <div id="p-wikibase-otherprojects" class="vector-menu mw-portlet mw-portlet-wikibase-otherprojects" > <div class="vector-menu-heading"> In other projects </div> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li id="t-wikibase" class="wb-otherproject-link wb-otherproject-wikibase-dataitem mw-list-item"><a href="https://www.wikidata.org/wiki/Special:EntityPage/Q2892636" title="Structured data on this page hosted by Wikidata [g]" accesskey="g"><span>Wikidata item</span></a></li> </ul> </div> </div> </div> </div> </div> </div> </nav> </div> </div> </div> <div class="vector-column-end"> <div class="vector-sticky-pinned-container"> <nav class="vector-page-tools-landmark" aria-label="Page tools"> <div id="vector-page-tools-pinned-container" class="vector-pinned-container"> </div> </nav> <nav class="vector-appearance-landmark" aria-label="Appearance"> <div id="vector-appearance-pinned-container" class="vector-pinned-container"> <div id="vector-appearance" class="vector-appearance vector-pinnable-element"> <div class="vector-pinnable-header vector-appearance-pinnable-header vector-pinnable-header-pinned" data-feature-name="appearance-pinned" data-pinnable-element-id="vector-appearance" data-pinned-container-id="vector-appearance-pinned-container" data-unpinned-container-id="vector-appearance-unpinned-container" > <div class="vector-pinnable-header-label">Appearance</div> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-pin-button" data-event-name="pinnable-header.vector-appearance.pin">move to sidebar</button> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-unpin-button" data-event-name="pinnable-header.vector-appearance.unpin">hide</button> </div> </div> </div> </nav> </div> </div> <div id="bodyContent" class="vector-body" aria-labelledby="firstHeading" data-mw-ve-target-container> <div class="vector-body-before-content"> <div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">High frequency of mutations within the genome of a cellular lineage</div> <p><b>Genome instability</b> (also <b>genetic instability</b> or <b>genomic instability</b>) refers to a high frequency of <a href="/wiki/Mutation" title="Mutation">mutations</a> within the genome of a <a href="/wiki/Cell_lineage" title="Cell lineage">cellular lineage</a>. These mutations can include changes in <a href="/wiki/Nucleic_acid_sequence" title="Nucleic acid sequence">nucleic acid sequences</a>, <a href="/wiki/Chromosomal_rearrangement" title="Chromosomal rearrangement">chromosomal rearrangements</a> or <a href="/wiki/Aneuploidy" title="Aneuploidy">aneuploidy</a>. Genome instability does occur in bacteria.<sup id="cite_ref-Darmon_1-0" class="reference"><a href="#cite_note-Darmon-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> In multicellular organisms genome instability is central to carcinogenesis,<sup id="cite_ref-Schmitt_2-0" class="reference"><a href="#cite_note-Schmitt-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> and in humans it is also a factor in some <a href="/wiki/Neurodegeneration" class="mw-redirect" title="Neurodegeneration">neurodegenerative</a> diseases such as <a href="/wiki/Amyotrophic_lateral_sclerosis" class="mw-redirect" title="Amyotrophic lateral sclerosis">amyotrophic lateral sclerosis</a> or the neuromuscular disease <a href="/wiki/Myotonic_dystrophy" title="Myotonic dystrophy">myotonic dystrophy</a>. </p><p>The sources of genome instability have only recently begun to be elucidated. A high frequency of externally caused DNA damage<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> can be one source of genome instability since DNA damage can cause inaccurate <a href="/wiki/Translesion" class="mw-redirect" title="Translesion">translesion</a> DNA synthesis past the damage or errors in repair, leading to <a href="/wiki/Mutation" title="Mutation">mutation</a>. Another source of genome instability may be <a href="/wiki/Epigenetics" title="Epigenetics">epigenetic</a> or <a href="/wiki/Mutation" title="Mutation">mutational</a> reductions in expression of DNA repair genes. Because <a href="/wiki/DNA_damage_(naturally_occurring)" title="DNA damage (naturally occurring)">endogenous (metabolically-caused) DNA damage</a> is very frequent, occurring on average more than 60,000 times a day in the genomes of human cells, any reduced DNA repair is likely an important source of genome instability. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Usual_genome_situation">Usual genome situation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=1" title="Edit section: Usual genome situation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Usually, all cells in an individual in a given species (plant or animal) show a constant number of <a href="/wiki/Chromosome" title="Chromosome">chromosomes</a>, which constitute what is known as the <a href="/wiki/Karyotype" title="Karyotype">karyotype</a> defining this species (see also <a href="/wiki/List_of_number_of_chromosomes_of_various_organisms" class="mw-redirect" title="List of number of chromosomes of various organisms">List of number of chromosomes of various organisms</a>), although some species present a very high karyotypic variability. In humans, mutations that would change an amino acid within the protein coding region of the genome occur at an average of only 0.35 per generation (less than one mutated protein per generation).<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> </p><p>Sometimes, in a species with a stable karyotype, random variations that modify the normal number of chromosomes may be observed. In other cases, there are structural alterations (e.g., <a href="/wiki/Chromosomal_translocation" title="Chromosomal translocation">chromosomal translocations</a>, <a href="/wiki/Deletion_(genetics)" title="Deletion (genetics)">deletions</a>) that modify the standard chromosomal complement. In these cases, it is indicated that the affected organism presents genome instability (also <i>genetic instability</i>, or even <i>chromosomic instability</i>). The process of genome instability often leads to a situation of <a href="/wiki/Aneuploidy" title="Aneuploidy">aneuploidy</a>, in which the cells present a chromosomic number that is either higher or lower than the normal complement for the species. </p> <div class="mw-heading mw-heading2"><h2 id="Causes_of_genome_instability">Causes of genome instability</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=2" title="Edit section: Causes of genome instability"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Replication_stress" class="mw-redirect" title="Replication stress">Replication stress</a></div> <div class="mw-heading mw-heading3"><h3 id="DNA_Replication_Defects">DNA Replication Defects</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=3" title="Edit section: DNA Replication Defects"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In the cell cycle, DNA is usually most vulnerable during replication. The <a href="/wiki/Replisome" title="Replisome">replisome</a> must be able to navigate obstacles such as tightly wound chromatin with bound proteins, single and double stranded breaks which can lead to the stalling of the replication fork. Each protein or enzyme in the <a href="/wiki/Replisome" title="Replisome">replisome</a> must perform its function well to result in a perfect copy of DNA. Mutations of proteins such as DNA polymerase or DNA ligase can lead to impairment of replication and lead to spontaneous chromosomal exchanges.<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> Proteins such as Tel1 and Mec1 (ATR, ATM in humans) can detect single and double-stranded breaks and recruit factors such as Rmr3 <a href="/wiki/Helicase" title="Helicase">helicase</a> to stabilize the replication fork in order to prevent its collapse. Mutations in Tel1, Mec1, and Rmr3 <a href="/wiki/Helicase" title="Helicase">helicase</a> result in a significant increase of chromosomal recombination. ATR responds specifically to stalled replication forks and single-stranded breaks resulting from UV damage while ATM responds directly to double-stranded breaks. These proteins also prevent progression into mitosis by inhibiting the firing of late replication origins until the DNA breaks are fixed by phosphorylating CHK1 and CHK2, which results in a signaling cascade arresting the cell in S-phase.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> For single stranded breaks, replication occurs until the location of the break, then the other strand is nicked to form a double stranded break, which can then be repaired by Break Induced Replication or homologous recombination using the sister <a href="/wiki/Chromatid" title="Chromatid">chromatid</a> as an error-free template.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> In addition to S-phase checkpoints, G1 and G2 checkpoints exist to check for transient DNA damage which could be caused by mutagens such as UV damage. An example is the Saccharomyces pombe gene rad9 which arrests the cells in late S/G2 phase in the presence of DNA damage caused by radiation. The yeast cells with defective rad9 failed to arrest following irradiation, continued cell division, and died rapidly; the cells with wild-type rad9 successfully arrested in late S/G2 phase and remained viable. The cells that arrested were able to survive due to the increased time in S/G2 phase allowing for DNA repair enzymes to function fully.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Fragile_Sites">Fragile Sites</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=4" title="Edit section: Fragile Sites"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>There are hotspots in the genome where DNA sequences are prone to gaps and breaks after inhibition of DNA synthesis such as in the aforementioned checkpoint arrest. These sites are called fragile sites, and can occur commonly as naturally present in most mammalian genomes or occur rarely as a result of mutations, such as DNA-repeat expansion. Rare fragile sites can lead to genetic disease such as fragile X mental retardation syndrome, myotonic dystrophy, Friedrich's ataxia, and Huntington's disease, most of which are caused by expansion of repeats at the DNA, RNA, or protein level.<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Although, seemingly harmful, these common fragile sites are conserved all the way to yeast and bacteria. These ubiquitous sites are characterized by trinucleotide repeats, most commonly CGG, CAG, GAA, and GCN. These trinucleotide repeats can form into hairpins, leading to difficulty of replication. Under <a href="/wiki/Replication_stress" class="mw-redirect" title="Replication stress">replication stress</a>, such as defective machinery or further DNA damage, DNA breaks and gaps can form at these fragile sites. Using a sister chromatid as repair is not a fool-proof backup as the surrounding DNA information of the n and n+1 repeat is virtually the same, leading to copy number variation. For example, the 16th copy of CGG might be mapped to the 13th copy of CGG in the sister chromatid since the surrounding DNA is both CGGCGGCGG..., leading to 3 extra copies of CGG in the final DNA sequence.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (February 2024)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading3"><h3 id="Transcription-associated_instability">Transcription-associated instability</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=5" title="Edit section: Transcription-associated instability"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In both E. coli and Saccharomyces pombe, transcription sites tend to have higher recombination and mutation rates. The coding or non-transcribed strand accumulates more mutations than the template strand. This is due to the fact that the coding strand is single-stranded during transcription, which is chemically more unstable than double-stranded DNA. During elongation of transcription, supercoiling can occur behind an elongating RNA polymerase, leading to single-stranded breaks. When the coding strand is single-stranded, it can also hybridize with itself, creating DNA secondary structures that can compromise replication. In E. coli, when attempting to transcribe GAA triplets such as those found in Friedrich's ataxia, the resulting RNA and template strand can form mismatched loops between different repeats, leaving the complementary segment in the coding strand available to form its own loops which impede replication.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Furthermore, replication of DNA and transcription of DNA are not temporally independent; they can occur at the same time and lead to collisions between the replication fork and RNA polymerase complex. In S. cerevisiae, Rrm3 helicase is found at highly transcribed genes in the yeast genome, which is recruited to stabilize a stalling replication fork as described above. This suggests that transcription is an obstacle to replication, which can lead to increased stress in the chromatin spanning the short distance between the unwound replication fork and transcription start site, potentially causing single-stranded DNA breaks. In yeast, proteins act as barriers at the 3' of the transcription unit to prevent further travel of the DNA replication fork.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Increase_Genetic_Variability">Increase Genetic Variability</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=6" title="Edit section: Increase Genetic Variability"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In some portions of the genome, variability is essential to survival. One such locale is the Ig genes. In a pre-B cell, the region consists of all V, D, and J segments. During development of the B cell, a specific V, D, and J segment is chosen to be spliced together to form the final gene, which is catalyzed by RAG1 and RAG2 recombinases. Activation-Induced Cytidine Deaminase (AID) then converts cytidine into uracil. Uracil normally does not exist in DNA, and thus the base is excised and the nick is converted into a double-stranded break which is repaired by non-homologous end joining (NHEJ). This procedure is very error-prone and leads to somatic hypermutation. This genomic instability is crucial in ensuring mammalian survival against infection. <a href="/wiki/V(D)J_recombination" title="V(D)J recombination">V, D, J recombination</a> can ensure millions of unique B-cell receptors; however, random repair by NHEJ introduces variation which can create a receptor that can bind with higher affinity to antigens.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="In_neuronal_and_neuromuscular_disease">In neuronal and neuromuscular disease</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=7" title="Edit section: In neuronal and neuromuscular disease"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Of about 200 neurological and neuromuscular disorders, 15 have a clear link to an inherited or acquired defect in one of the DNA repair pathways or excessive genotoxic oxidative stress.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Five of them (<a href="/wiki/Xeroderma_pigmentosum" title="Xeroderma pigmentosum">xeroderma pigmentosum</a>, <a href="/wiki/Cockayne%27s_syndrome" class="mw-redirect" title="Cockayne's syndrome">Cockayne's syndrome</a>, <a href="/wiki/Trichothiodystrophy" title="Trichothiodystrophy">trichothiodystrophy</a>, <a href="/wiki/Down%27s_syndrome" class="mw-redirect" title="Down's syndrome">Down's syndrome</a>, and <a href="/wiki/Triple-A_syndrome" title="Triple-A syndrome">triple-A syndrome</a>) have a defect in the DNA nucleotide excision repair pathway. Six (<a href="/wiki/Spinocerebellar_ataxia" title="Spinocerebellar ataxia">spinocerebellar ataxia</a> with axonal neuropathy-1, <a href="/wiki/Huntington%27s_disease" title="Huntington's disease">Huntington's disease</a>, <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a>, <a href="/wiki/Parkinson%27s_disease" title="Parkinson's disease">Parkinson's disease</a>, <a href="/wiki/Down%27s_syndrome" class="mw-redirect" title="Down's syndrome">Down's syndrome</a> and <a href="/wiki/Amyotrophic_lateral_sclerosis" class="mw-redirect" title="Amyotrophic lateral sclerosis">amyotrophic lateral sclerosis</a>) seem to result from increased oxidative stress, and the inability of the base excision repair pathway to handle the damage to DNA that this causes. Four of them (Huntington's disease, various <a href="/wiki/Spinocerebellar_ataxia" title="Spinocerebellar ataxia">spinocerebellar ataxias</a>, <a href="/wiki/Friedreich%27s_ataxia" title="Friedreich's ataxia">Friedreich's ataxia</a> and <a href="/wiki/Myotonic_dystrophy" title="Myotonic dystrophy">myotonic dystrophy</a> types 1 and 2) often have an unusual expansion of repeat sequences in DNA, likely attributable to genome instability. Four (<a href="/wiki/Ataxia-telangiectasia" class="mw-redirect" title="Ataxia-telangiectasia">ataxia-telangiectasia</a>, ataxia-telangiectasia-like disorder, <a href="/wiki/Nijmegen_breakage_syndrome" title="Nijmegen breakage syndrome">Nijmegen breakage syndrome</a> and Alzheimer's disease) are defective in genes involved in repairing DNA double-strand breaks. Overall, it seems that oxidative stress is a major cause of genomic instability in the brain. A particular neurological disease arises when a pathway that normally prevents oxidative stress is deficient, or a DNA repair pathway that normally repairs damage caused by oxidative stress is deficient.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (February 2024)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading2"><h2 id="In_cancer">In cancer</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=8" title="Edit section: In cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In <a href="/wiki/Cancer" title="Cancer">cancer</a>, genome instability can occur prior to or as a consequence of transformation.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> Genome instability can refer to the accumulation of extra copies of <a href="/wiki/DNA" title="DNA">DNA</a> or <a href="/wiki/Chromosome" title="Chromosome">chromosomes</a>, <a href="/wiki/Chromosomal_translocation" title="Chromosomal translocation">chromosomal translocations</a>, <a href="/wiki/Chromosomal_inversion" title="Chromosomal inversion">chromosomal inversions</a>, chromosome <a href="/wiki/Deletion_(genetics)" title="Deletion (genetics)">deletions</a>, single-strand breaks in DNA, <a href="/wiki/Double-strand_break" class="mw-redirect" title="Double-strand break">double-strand breaks</a> in DNA, the intercalation of foreign substances into the DNA double helix, or any abnormal changes in DNA tertiary structure that can cause either the loss of DNA, or the misexpression of genes. Situations of genome instability (as well as aneuploidy) are common in cancer cells, and they are considered a "hallmark" for these cells. The unpredictable nature of these events are also a main contributor to the <a href="/wiki/Tumour_heterogeneity" title="Tumour heterogeneity">heterogeneity</a> observed among tumour cells.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (February 2024)">citation needed</span></a></i>]</sup> </p><p>It is currently accepted that sporadic tumors (non-familial ones) are originated due to the accumulation of several genetic errors.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> An average cancer of the breast or colon can have about 60 to 70 protein altering mutations, of which about 3 or 4 may be "driver" mutations, and the remaining ones may be "passenger" mutations<sup id="cite_ref-Vogelstein_17-0" class="reference"><a href="#cite_note-Vogelstein-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> Any genetic or epigenetic lesion increasing the <a href="/wiki/Mutation" title="Mutation">mutation</a> rate will have as a consequence an increase in the acquisition of new mutations, increasing then the probability to develop a tumor.<sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> During the process of <a href="/wiki/Tumorogenesis" class="mw-redirect" title="Tumorogenesis">tumorogenesis</a>, it is known that <a href="/wiki/Diploid" class="mw-redirect" title="Diploid">diploid</a> cells acquire mutations in genes responsible for maintaining genome integrity (<i><a href="/wiki/Caretaker_gene" title="Caretaker gene">caretaker genes</a></i>), as well as in genes that are directly controlling cellular proliferation (<i><a href="/wiki/Gatekeeper_gene" class="mw-redirect" title="Gatekeeper gene">gatekeeper genes</a></i>).<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> Genetic instability can originate due to deficiencies in DNA repair, or due to loss or gain of chromosomes, or due to large scale chromosomal reorganizations. Losing genetic stability will favour tumor development, because it favours the generation of mutants that can be selected by the environment.<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p><p>The <a href="/wiki/Tumor_microenvironment" title="Tumor microenvironment">tumor microenvironment</a> has an inhibitory effect on <a href="/wiki/DNA_repair" title="DNA repair">DNA repair</a> pathways contributing to genomic instability, which promotes tumor survival, proliferation, and malignant transformation.<sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Low_frequency_of_mutations_without_cancer">Low frequency of mutations without cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=9" title="Edit section: Low frequency of mutations without cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The protein coding regions of the human genome, collectively called the <a href="/wiki/Exome" title="Exome">exome</a>, constitutes only 1.5% of the total genome.<sup id="cite_ref-pmid11237011_22-0" class="reference"><a href="#cite_note-pmid11237011-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> As pointed out above, ordinarily there are only an average of 0.35 mutations in the exome per generation (parent to child) in humans. In the entire genome (including non-protein coding regions) there are only about 70 new mutations per generation in humans.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Cause_of_mutations_in_cancer">Cause of mutations in cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=10" title="Edit section: Cause of mutations in cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The likely major underlying cause of mutations in cancer is DNA damage.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="removed citation to predatory publisher content (December 2019)">citation needed</span></a></i>]</sup> For example, in the case of lung cancer, DNA damage is caused by agents in <a href="/wiki/Exogeny" title="Exogeny">exogenous</a> <a href="/wiki/Genotoxicity" title="Genotoxicity">genotoxic</a> tobacco smoke (e.g. <a href="/wiki/Acrolein" title="Acrolein">acrolein</a>, formaldehyde, <a href="/wiki/Acrylonitrile" title="Acrylonitrile">acrylonitrile</a>, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene).<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> <a href="/wiki/DNA_damage_(naturally_occurring)" title="DNA damage (naturally occurring)">Endogenous (metabolically-caused) DNA damage</a> is also very frequent, occurring on average more than 60,000 times a day in the genomes of human cells (see <a href="/wiki/DNA_damage_(naturally_occurring)" title="DNA damage (naturally occurring)">DNA damage (naturally occurring)</a>). Externally and endogenously caused damages may be converted into mutations by inaccurate <a href="/wiki/Translesion_synthesis" class="mw-redirect" title="Translesion synthesis">translesion synthesis</a> or inaccurate DNA repair (e.g. by <a href="/wiki/Non-homologous_end_joining" title="Non-homologous end joining">non-homologous end joining</a>). In addition, DNA damages can also give rise to <a href="/wiki/Epigenetics" title="Epigenetics">epigenetic</a> alterations during DNA repair.<sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> Both mutations and epigenetic alterations (epimutations) can contribute to progression to <a href="/wiki/Neoplasm#Malignant_neoplasm" title="Neoplasm">cancer</a>. </p> <div class="mw-heading mw-heading3"><h3 id="Very_frequent_mutations_in_cancer">Very frequent mutations in cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=11" title="Edit section: Very frequent mutations in cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>As noted above, about 3 or 4 driver mutations and 60 passenger mutations occur in the exome (protein coding region) of a cancer.<sup id="cite_ref-Vogelstein_17-1" class="reference"><a href="#cite_note-Vogelstein-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> However, a much larger number of mutations occur in the <a href="/wiki/Noncoding_DNA" class="mw-redirect" title="Noncoding DNA">non-protein-coding regions</a> of DNA. The average number of DNA sequence mutations in the entire genome of a breast cancer tissue sample is about 20,000.<sup id="cite_ref-pmid22492626_29-0" class="reference"><a href="#cite_note-pmid22492626-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> In an average melanoma tissue sample (where melanomas have a higher <a href="/wiki/Exome" title="Exome">exome</a> mutation frequency<sup id="cite_ref-Vogelstein_17-2" class="reference"><a href="#cite_note-Vogelstein-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup>) the total number of DNA sequence mutations is about 80,000.<sup id="cite_ref-pmid22622578_30-0" class="reference"><a href="#cite_note-pmid22622578-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Cause_of_high_frequency_of_mutations_in_cancer">Cause of high frequency of mutations in cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=12" title="Edit section: Cause of high frequency of mutations in cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The high frequency of mutations in the total genome within cancers suggests that, often, an early carcinogenic alteration may be a deficiency in DNA repair. Mutation rates substantially increase (sometimes by 100-fold) in cells defective in <a href="/wiki/DNA_mismatch_repair" title="DNA mismatch repair">DNA mismatch repair</a><sup id="cite_ref-Narayanan_31-0" class="reference"><a href="#cite_note-Narayanan-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Hegan_32-0" class="reference"><a href="#cite_note-Hegan-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> or in <a href="/wiki/Homologous_recombination" title="Homologous recombination">homologous recombinational</a> <a href="/wiki/DNA_repair" title="DNA repair">DNA repair</a>.<sup id="cite_ref-Tutt_33-0" class="reference"><a href="#cite_note-Tutt-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> Also, chromosomal rearrangements and aneuploidy increase in humans defective in DNA repair gene <a href="/wiki/Bloom_syndrome_protein" title="Bloom syndrome protein">BLM</a>.<sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> </p><p>A deficiency in DNA repair itself can allow DNA damages to accumulate, and error-prone <a href="/wiki/DNA_repair" title="DNA repair">translesion synthesis</a> past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to <a href="/wiki/Epigenetics" title="Epigenetics">epigenetic alterations or epimutations</a>. While a mutation or epimutation in a DNA repair gene itself would not confer a selective advantage, such a repair defect may be carried along as a passenger in a cell when the cell acquires an additional mutation/epimutation that does provide a proliferative advantage. Such cells, with both proliferative advantages and one or more DNA repair defects (causing a very high mutation rate), likely give rise to the 20,000 to 80,000 total genome mutations frequently seen in cancers.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (February 2024)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading3"><h3 id="DNA_repair_deficiency_in_cancer">DNA repair deficiency in cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=13" title="Edit section: DNA repair deficiency in cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In somatic cells, deficiencies in DNA repair sometimes arise by mutations in DNA repair genes, but much more often are due to epigenetic reductions in expression of DNA repair genes. Thus, in a sequence of 113 colorectal cancers, only four had somatic missense mutations in the DNA repair gene MGMT, while the majority of these cancers had reduced MGMT expression due to methylation of the MGMT promoter region.<sup id="cite_ref-pmid15888787_35-0" class="reference"><a href="#cite_note-pmid15888787-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> Five reports, listed in the article <a href="/wiki/Epigenetics" title="Epigenetics">Epigenetics</a> (see section "DNA repair epigenetics in cancer") presented evidence that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region. </p><p>Similarly, for 119 cases of colorectal cancers classified as mismatch repair deficient and lacking DNA repair gene PMS2 expression, Pms2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1).<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> The other 10 cases of loss of PMS2 expression were likely due to epigenetic overexpression of the microRNA, miR-155, which down-regulates MLH1.<sup id="cite_ref-37" class="reference"><a href="#cite_note-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> </p><p>In <a href="/wiki/Cancer_epigenetics" title="Cancer epigenetics">cancer epigenetics</a> (see section <a href="/wiki/Cancer_epigenetics#Frequencies_of_epimutations_in_DNA_repair_genes" title="Cancer epigenetics">Frequencies of epimutations in DNA repair genes</a>), there is a partial listing of epigenetic deficiencies found in DNA repair genes in sporadic cancers. These include frequencies of between 13–100% of epigenetic defects in genes <a href="/wiki/BRCA1" title="BRCA1">BRCA1</a>, <a href="/wiki/WRN_(gene)" class="mw-redirect" title="WRN (gene)">WRN</a>, <a href="/wiki/FANCB" title="FANCB">FANCB</a>, <a href="/wiki/FANCF" title="FANCF">FANCF</a>, <a href="/wiki/O-6-methylguanine-DNA_methyltransferase" class="mw-redirect" title="O-6-methylguanine-DNA methyltransferase">MGMT</a>, <a href="/wiki/MLH1" title="MLH1">MLH1</a>, <a href="/wiki/MSH2" title="MSH2">MSH2</a>, <a href="/wiki/MSH4" title="MSH4">MSH4</a>, <a href="/wiki/ERCC1" title="ERCC1">ERCC1</a>, XPF, <a href="/wiki/NEIL1" title="NEIL1">NEIL1</a> and <a href="/wiki/Ataxia_telangiectasia_mutated" class="mw-redirect" title="Ataxia telangiectasia mutated">ATM</a> located in cancers including breast, ovarian, colorectal and head and neck. Two or three epigenetic deficiencies in expression of ERCC1, XPF and/or PMS2 were found to occur simultaneously in the majority of the 49 colon cancers evaluated.<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> Some of these DNA repair deficiencies can be caused by epimutations in <a href="/wiki/MicroRNA" title="MicroRNA">microRNAs</a> as summarized in the <a href="/wiki/MicroRNA" title="MicroRNA">MicroRNA</a> article section titled <a href="/wiki/MicroRNA#miRNA,_DNA_repair_and_cancer" title="MicroRNA">miRNA, DNA repair and cancer</a>. </p> <div class="mw-heading mw-heading3"><h3 id="Lymphomas_as_a_consequence_of_genome_instability">Lymphomas as a consequence of genome instability</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=14" title="Edit section: Lymphomas as a consequence of genome instability"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Cancers usually result from disruption of a tumor repressor or dysregulation of an oncogene. Knowing that B-cells experience DNA breaks during development can give insight to the genome of lymphomas. Many types of lymphoma are caused by chromosomal translocation, which can arise from breaks in DNA, leading to incorrect joining. In Burkitt's lymphoma, <a href="/wiki/C-myc" class="mw-redirect" title="C-myc">c-myc</a>, an oncogene encoding a transcription factor, is translocated to a position after the promoter of the immunoglobulin gene, leading to dysregulation of c-myc transcription. Since immunoglobulins are essential to a lymphocyte and highly expressed to increase detection of antigens, c-myc is then also highly expressed, leading to transcription of its <a href="/wiki/Biological_target" title="Biological target">targets</a>, which are involved in cell proliferation. <a href="/wiki/Mantle_cell_lymphoma" title="Mantle cell lymphoma">Mantle cell lymphoma</a> is characterized by fusion of <a href="/wiki/Cyclin_D1" title="Cyclin D1">cyclin D1</a> to the immunoglobulin locus. Cyclin D1 inhibits Rb, a tumor suppressor, leading to tumorigenesis. <a href="/wiki/Follicular_lymphoma" title="Follicular lymphoma">Follicular lymphoma</a> results from the translocation of the immunoglobulin promoter to the Bcl-2 gene, giving rise to high levels of Bcl-2 protein, which inhibits apoptosis. DNA-damaged B-cells no longer undergo apoptosis, leading to further mutations which could affect driver genes, leading to tumorigenesis.<sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> The location of translocation in the oncogene shares structural properties of the target regions of <a href="/wiki/Activation-induced_cytidine_deaminase" title="Activation-induced cytidine deaminase">AID</a>, suggesting that the oncogene was a potential target of AID, leading to a double-stranded break that was translocated to the immunoglobulin gene locus through <a href="/wiki/Non-homologous_end_joining" title="Non-homologous end joining">NHEJ</a> repair.<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="In_aging">In aging</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=15" title="Edit section: In aging"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/Hallmarks_of_aging#Genome_instability" title="Hallmarks of aging">Hallmarks of aging > Genome instability</a></div> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Genome_instability&action=edit&section=16" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 30em;"> <ol class="references"> <li id="cite_note-Darmon-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-Darmon_1-0">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFDarmonLeach2014" class="citation journal cs1">Darmon, E; Leach, DRF (2014). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957733">"Bacterial Genome Instability"</a>. <i>Microbiol. Mol. Biol. Rev</i>. <b>78</b> (1): 1–39. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1128%2FMMBR.00035-13">10.1128/MMBR.00035-13</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957733">3957733</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/24600039">24600039</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Microbiol.+Mol.+Biol.+Rev.&rft.atitle=Bacterial+Genome+Instability&rft.volume=78&rft.issue=1&rft.pages=1-39&rft.date=2014&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3957733%23id-name%3DPMC&rft_id=info%3Apmid%2F24600039&rft_id=info%3Adoi%2F10.1128%2FMMBR.00035-13&rft.aulast=Darmon&rft.aufirst=E&rft.au=Leach%2C+DRF&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3957733&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-Schmitt-2"><span class="mw-cite-backlink"><b><a href="#cite_ref-Schmitt_2-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSchmittPrindleLoeb2012" class="citation journal cs1">Schmitt, MW; Prindle, MJ; Loeb, LA (2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674777">"Implications of genetic heterogeneity in cancer"</a>. <i>Ann N Y Acad Sci</i>. <b>1267</b> (1): 110–116. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2012NYASA1267..110S">2012NYASA1267..110S</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1749-6632.2012.06590.x">10.1111/j.1749-6632.2012.06590.x</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674777">3674777</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22954224">22954224</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Ann+N+Y+Acad+Sci&rft.atitle=Implications+of+genetic+heterogeneity+in+cancer&rft.volume=1267&rft.issue=1&rft.pages=110-116&rft.date=2012&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3674777%23id-name%3DPMC&rft_id=info%3Apmid%2F22954224&rft_id=info%3Adoi%2F10.1111%2Fj.1749-6632.2012.06590.x&rft_id=info%3Abibcode%2F2012NYASA1267..110S&rft.aulast=Schmitt&rft.aufirst=MW&rft.au=Prindle%2C+MJ&rft.au=Loeb%2C+LA&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3674777&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-3"><span class="mw-cite-backlink"><b><a href="#cite_ref-3">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMøller2005" class="citation journal cs1">Møller, P (2005). "Genotoxicity of environmental agents assessed by the alkaline comet assay". <i>Basic Clin Pharmacol Toxicol</i>. <b>96</b> (Suppl 1): 1–42. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/15859009">15859009</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Basic+Clin+Pharmacol+Toxicol&rft.atitle=Genotoxicity+of+environmental+agents+assessed+by+the+alkaline+comet+assay&rft.volume=96&rft.issue=Suppl+1&rft.pages=1-42&rft.date=2005&rft_id=info%3Apmid%2F15859009&rft.aulast=M%C3%B8ller&rft.aufirst=P&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-4"><span class="mw-cite-backlink"><b><a href="#cite_ref-4">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFKeightley_PD2012" class="citation journal cs1">Keightley PD (February 2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276617">"Rates and fitness consequences of new mutations in humans"</a>. <i>Genetics</i>. <b>190</b> (2): 295–304. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1534%2Fgenetics.111.134668">10.1534/genetics.111.134668</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276617">3276617</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22345605">22345605</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Rates+and+fitness+consequences+of+new+mutations+in+humans&rft.volume=190&rft.issue=2&rft.pages=295-304&rft.date=2012-02&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3276617%23id-name%3DPMC&rft_id=info%3Apmid%2F22345605&rft_id=info%3Adoi%2F10.1534%2Fgenetics.111.134668&rft.au=Keightley+PD&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3276617&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-5"><span class="mw-cite-backlink"><b><a href="#cite_ref-5">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAguileraKlein1998" class="citation journal cs1">Aguilera, A; Klein, H. L. (Aug 1998). "Genetic control of intrachromosomal recombination in Saccharomyces cerevisiae. I. Isolation and genetic characterization of hyper-recombination mutations". <i>Genetics</i>. <b>4</b> (4): 779–790.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Genetic+control+of+intrachromosomal+recombination+in+Saccharomyces+cerevisiae.+I.+Isolation+and+genetic+characterization+of+hyper-recombination+mutations&rft.volume=4&rft.issue=4&rft.pages=779-790&rft.date=1998-08&rft.aulast=Aguilera&rft.aufirst=A&rft.au=Klein%2C+H.+L.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-6"><span class="mw-cite-backlink"><b><a href="#cite_ref-6">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCobb2005" class="citation journal cs1">Cobb, J. A. (Dec 2005). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315408">"Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations"</a>. <i>Genes & Development</i>. <b>19</b> (24): 3055–3069. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1101%2Fgad.361805">10.1101/gad.361805</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315408">1315408</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16357221">16357221</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Genes+%26+Development&rft.atitle=Replisome+instability%2C+fork+collapse%2C+and+gross+chromosomal+rearrangements+arise+synergistically+from+Mec1+kinase+and+RecQ+helicase+mutations&rft.volume=19&rft.issue=24&rft.pages=3055-3069&rft.date=2005-12&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1315408%23id-name%3DPMC&rft_id=info%3Apmid%2F16357221&rft_id=info%3Adoi%2F10.1101%2Fgad.361805&rft.aulast=Cobb&rft.aufirst=J.+A.&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1315408&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-7"><span class="mw-cite-backlink"><b><a href="#cite_ref-7">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCortes-LedesmaAguilera2006" class="citation journal cs1">Cortes-Ledesma, Felipe; Aguilera, Andres (Sep 2006). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559660">"Double-strand breaks arising from replication through a nick are repaired by cohesin-dependent sister-chromatid exchange"</a>. <i>EMBO Reports</i>. <b>7</b> (9): 919–926. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fsj.embor.7400774">10.1038/sj.embor.7400774</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559660">1559660</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16888651">16888651</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=EMBO+Reports&rft.atitle=Double-strand+breaks+arising+from+replication+through+a+nick+are+repaired+by+cohesin-dependent+sister-chromatid+exchange&rft.volume=7&rft.issue=9&rft.pages=919-926&rft.date=2006-09&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1559660%23id-name%3DPMC&rft_id=info%3Apmid%2F16888651&rft_id=info%3Adoi%2F10.1038%2Fsj.embor.7400774&rft.aulast=Cortes-Ledesma&rft.aufirst=Felipe&rft.au=Aguilera%2C+Andres&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1559660&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-8"><span class="mw-cite-backlink"><b><a href="#cite_ref-8">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFWeinertHartwell1993" class="citation journal cs1">Weinert, T. A.; Hartwell, L. H. (May 1993). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1205445">"Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint"</a>. <i>Genetics</i>. <b>134</b> (1): 63–80. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1093%2Fgenetics%2F134.1.63">10.1093/genetics/134.1.63</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1205445">1205445</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/8514150">8514150</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Cell+cycle+arrest+of+cdc+mutants+and+specificity+of+the+RAD9+checkpoint&rft.volume=134&rft.issue=1&rft.pages=63-80&rft.date=1993-05&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1205445%23id-name%3DPMC&rft_id=info%3Apmid%2F8514150&rft_id=info%3Adoi%2F10.1093%2Fgenetics%2F134.1.63&rft.aulast=Weinert&rft.aufirst=T.+A.&rft.au=Hartwell%2C+L.+H.&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1205445&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-9"><span class="mw-cite-backlink"><b><a href="#cite_ref-9">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFDurkinGlover2007" class="citation journal cs1">Durkin, Sandra G.; Glover, Thomas W. (Dec 2007). "Chromosome Fragile Sites". <i>Annual Review of Genetics</i>. <b>41</b> (1): 169–192. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1146%2Fannurev.genet.41.042007.165900">10.1146/annurev.genet.41.042007.165900</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17608616">17608616</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Annual+Review+of+Genetics&rft.atitle=Chromosome+Fragile+Sites&rft.volume=41&rft.issue=1&rft.pages=169-192&rft.date=2007-12&rft_id=info%3Adoi%2F10.1146%2Fannurev.genet.41.042007.165900&rft_id=info%3Apmid%2F17608616&rft.aulast=Durkin&rft.aufirst=Sandra+G.&rft.au=Glover%2C+Thomas+W.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-10"><span class="mw-cite-backlink"><b><a href="#cite_ref-10">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGrabczykMancusoSammarco2007" class="citation journal cs1">Grabczyk, E.; Mancuso, M.; Sammarco, M. C. (Aug 2007). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2018641">"A persistent RNA-DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro"</a>. <i>Nucleic Acids Research</i>. <b>35</b> (16): 5351–5359. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1093%2Fnar%2Fgkm589">10.1093/nar/gkm589</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2018641">2018641</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17693431">17693431</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=A+persistent+RNA-DNA+hybrid+formed+by+transcription+of+the+Friedreich+ataxia+triplet+repeat+in+live+bacteria%2C+and+by+T7+RNAP+in+vitro&rft.volume=35&rft.issue=16&rft.pages=5351-5359&rft.date=2007-08&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2018641%23id-name%3DPMC&rft_id=info%3Apmid%2F17693431&rft_id=info%3Adoi%2F10.1093%2Fnar%2Fgkm589&rft.aulast=Grabczyk&rft.aufirst=E.&rft.au=Mancuso%2C+M.&rft.au=Sammarco%2C+M.+C.&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2018641&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-11"><span class="mw-cite-backlink"><b><a href="#cite_ref-11">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFTrautingerJaktajiRusakovaLloyd2005" class="citation journal cs1">Trautinger, Brigitte W.; Jaktaji, Razieh P.; Rusakova, Ekaterina; Lloyd, Robert G. (July 2005). <a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.molcel.2005.06.004">"RNA Polymerase Modulators and DNA Repair Activities Resolve Conflicts between DNA Replication and Transcription"</a>. <i>Molecular Cell</i>. <b>19</b> (2): 247–258. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.molcel.2005.06.004">10.1016/j.molcel.2005.06.004</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16039593">16039593</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Molecular+Cell&rft.atitle=RNA+Polymerase+Modulators+and+DNA+Repair+Activities+Resolve+Conflicts+between+DNA+Replication+and+Transcription&rft.volume=19&rft.issue=2&rft.pages=247-258&rft.date=2005-07&rft_id=info%3Adoi%2F10.1016%2Fj.molcel.2005.06.004&rft_id=info%3Apmid%2F16039593&rft.aulast=Trautinger&rft.aufirst=Brigitte+W.&rft.au=Jaktaji%2C+Razieh+P.&rft.au=Rusakova%2C+Ekaterina&rft.au=Lloyd%2C+Robert+G.&rft_id=https%3A%2F%2Fdoi.org%2F10.1016%252Fj.molcel.2005.06.004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-12"><span class="mw-cite-backlink"><b><a href="#cite_ref-12">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSchraderGuikemaLinehanSelsing2007" class="citation journal cs1">Schrader, Carol E.; Guikema, Jeroen E. J.; Linehan, Erin K.; Selsing, Erik; Stavnezer, Janet (Nov 2007). <a rel="nofollow" class="external text" href="https://doi.org/10.4049%2Fjimmunol.179.9.6064">"Activation-induced cytidine deaminase-dependent DNA breaks in class switch recombination occur during G1 phase of the cell cycle and depend upon mismatch repair"</a>. <i>Journal of Immunology</i>. <b>179</b> (9): 6064–6071. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.4049%2Fjimmunol.179.9.6064">10.4049/jimmunol.179.9.6064</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17947680">17947680</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Activation-induced+cytidine+deaminase-dependent+DNA+breaks+in+class+switch+recombination+occur+during+G1+phase+of+the+cell+cycle+and+depend+upon+mismatch+repair&rft.volume=179&rft.issue=9&rft.pages=6064-6071&rft.date=2007-11&rft_id=info%3Adoi%2F10.4049%2Fjimmunol.179.9.6064&rft_id=info%3Apmid%2F17947680&rft.aulast=Schrader&rft.aufirst=Carol+E.&rft.au=Guikema%2C+Jeroen+E.+J.&rft.au=Linehan%2C+Erin+K.&rft.au=Selsing%2C+Erik&rft.au=Stavnezer%2C+Janet&rft_id=https%3A%2F%2Fdoi.org%2F10.4049%252Fjimmunol.179.9.6064&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-13"><span class="mw-cite-backlink"><b><a href="#cite_ref-13">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSubba_Rao2007" class="citation journal cs1">Subba Rao, K (2007). "Mechanisms of disease: DNA repair defects and neurological disease". <i>Nat Clin Pract Neurol</i>. <b>3</b> (3): 162–72. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fncpneuro0448">10.1038/ncpneuro0448</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17342192">17342192</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:12930631">12930631</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nat+Clin+Pract+Neurol&rft.atitle=Mechanisms+of+disease%3A+DNA+repair+defects+and+neurological+disease&rft.volume=3&rft.issue=3&rft.pages=162-72&rft.date=2007&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A12930631%23id-name%3DS2CID&rft_id=info%3Apmid%2F17342192&rft_id=info%3Adoi%2F10.1038%2Fncpneuro0448&rft.aulast=Subba+Rao&rft.aufirst=K&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-14"><span class="mw-cite-backlink"><b><a href="#cite_ref-14">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFJeppesenBohrStevnsner2011" class="citation journal cs1">Jeppesen, DK; Bohr, VA; Stevnsner, T (2011). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123739">"DNA repair deficiency in neurodegeneration"</a>. <i>Prog Neurobiol</i>. <b>94</b> (2): 166–200. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.pneurobio.2011.04.013">10.1016/j.pneurobio.2011.04.013</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123739">3123739</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21550379">21550379</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Prog+Neurobiol&rft.atitle=DNA+repair+deficiency+in+neurodegeneration&rft.volume=94&rft.issue=2&rft.pages=166-200&rft.date=2011&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3123739%23id-name%3DPMC&rft_id=info%3Apmid%2F21550379&rft_id=info%3Adoi%2F10.1016%2Fj.pneurobio.2011.04.013&rft.aulast=Jeppesen&rft.aufirst=DK&rft.au=Bohr%2C+VA&rft.au=Stevnsner%2C+T&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3123739&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-15"><span class="mw-cite-backlink"><b><a href="#cite_ref-15">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCorcos2012" class="citation cs2">Corcos, D. (2012), "Unbalanced replication as a major source of genetic instability in cancer cells", <i>American Journal of Blood Research</i>, <b>2</b> (3): 160–9, <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484411">3484411</a></span>, <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23119227">23119227</a></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=American+Journal+of+Blood+Research&rft.atitle=Unbalanced+replication+as+a+major+source+of+genetic+instability+in+cancer+cells&rft.volume=2&rft.issue=3&rft.pages=160-9&rft.date=2012&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3484411%23id-name%3DPMC&rft_id=info%3Apmid%2F23119227&rft.aulast=Corcos&rft.aufirst=D.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-16"><span class="mw-cite-backlink"><b><a href="#cite_ref-16">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFStorchovaPellman2004" class="citation cs2">Storchova, Z.; Pellman, D. (2004), "From polyploidy to aneuploidy, genome instability and cancer", <i>Nat Rev Mol Cell Biol</i>, <b>5</b> (1): 45–54, <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fnrm1276">10.1038/nrm1276</a>, <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/14708009">14708009</a>, <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:11985415">11985415</a></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nat+Rev+Mol+Cell+Biol&rft.atitle=From+polyploidy+to+aneuploidy%2C+genome+instability+and+cancer&rft.volume=5&rft.issue=1&rft.pages=45-54&rft.date=2004&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A11985415%23id-name%3DS2CID&rft_id=info%3Apmid%2F14708009&rft_id=info%3Adoi%2F10.1038%2Fnrm1276&rft.aulast=Storchova&rft.aufirst=Z.&rft.au=Pellman%2C+D.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-Vogelstein-17"><span class="mw-cite-backlink">^ <a href="#cite_ref-Vogelstein_17-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Vogelstein_17-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Vogelstein_17-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFVogelstein_BPapadopoulos_NVelculescu_VEZhou_S2013" class="citation journal cs1">Vogelstein B; Papadopoulos N; Velculescu VE; Zhou S; Diaz LA; Kinzler KW (March 2013). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749880">"Cancer genome landscapes"</a>. <i>Science</i>. <b>339</b> (6127): 1546–58. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2013Sci...339.1546V">2013Sci...339.1546V</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1126%2Fscience.1235122">10.1126/science.1235122</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749880">3749880</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23539594">23539594</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Science&rft.atitle=Cancer+genome+landscapes&rft.volume=339&rft.issue=6127&rft.pages=1546-58&rft.date=2013-03&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3749880%23id-name%3DPMC&rft_id=info%3Apmid%2F23539594&rft_id=info%3Adoi%2F10.1126%2Fscience.1235122&rft_id=info%3Abibcode%2F2013Sci...339.1546V&rft.au=Vogelstein+B&rft.au=Papadopoulos+N&rft.au=Velculescu+VE&rft.au=Zhou+S&rft.au=Diaz+LA&rft.au=Kinzler+KW&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3749880&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-18"><span class="mw-cite-backlink"><b><a href="#cite_ref-18">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFNowakKomarovaSenguptaJallepalli2002" class="citation cs2">Nowak, M. A.; <a href="/wiki/Natalia_Komarova" title="Natalia Komarova">Komarova, N. L.</a>; Sengupta, A.; Jallepalli, P.V.; Shih, I.M.; Vogelstein, B.; Lengauer, C. (2002), "The role of chromosomal instability in tumor initiation", <i>Proc. Natl. Acad. Sci. USA</i>, <b>99</b> (25): 16226–31, <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2002PNAS...9916226N">2002PNAS...9916226N</a>, <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1073%2Fpnas.202617399">10.1073/pnas.202617399</a></span>, <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC138593">138593</a></span>, <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/12446840">12446840</a></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Proc.+Natl.+Acad.+Sci.+USA&rft.atitle=The+role+of+chromosomal+instability+in+tumor+initiation&rft.volume=99&rft.issue=25&rft.pages=16226-31&rft.date=2002&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC138593%23id-name%3DPMC&rft_id=info%3Apmid%2F12446840&rft_id=info%3Adoi%2F10.1073%2Fpnas.202617399&rft_id=info%3Abibcode%2F2002PNAS...9916226N&rft.aulast=Nowak&rft.aufirst=M.+A.&rft.au=Komarova%2C+N.+L.&rft.au=Sengupta%2C+A.&rft.au=Jallepalli%2C+P.V.&rft.au=Shih%2C+I.M.&rft.au=Vogelstein%2C+B.&rft.au=Lengauer%2C+C.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-19"><span class="mw-cite-backlink"><b><a href="#cite_ref-19">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFKinzlerVogelstein1997" class="citation cs2">Kinzler, K. W.; Vogelstein, B. (April 1997), "Cancer-susceptibility genes. Gatekeepers and caretakers", <i>Nature</i>, <b>386</b> (6627): 761–3, <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1038%2F386761a0">10.1038/386761a0</a></span>, <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/9126728">9126728</a></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Cancer-susceptibility+genes.+Gatekeepers+and+caretakers&rft.volume=386&rft.issue=6627&rft.pages=761-3&rft.date=1997-04&rft_id=info%3Adoi%2F10.1038%2F386761a0&rft_id=info%3Apmid%2F9126728&rft.aulast=Kinzler&rft.aufirst=K.+W.&rft.au=Vogelstein%2C+B.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-20"><span class="mw-cite-backlink"><b><a href="#cite_ref-20">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCahillKinzlerVogelsteinLengauer1999" class="citation cs2">Cahill, D. P.; Kinzler, K. W.; Vogelstein, B.; Lengauer, C. (1999), "Genetic instability and darwinian selection in tumours", <i>Trends Cell Biol.</i>, <b>9</b> (12): M57–M60, <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1016%2FS0168-9525%2899%2901874-0">10.1016/S0168-9525(99)01874-0</a></span>, <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/10611684">10611684</a></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Trends+Cell+Biol.&rft.atitle=Genetic+instability+and+darwinian+selection+in+tumours&rft.volume=9&rft.issue=12&rft.pages=M57-M60&rft.date=1999&rft_id=info%3Adoi%2F10.1016%2FS0168-9525%2899%2901874-0&rft_id=info%3Apmid%2F10611684&rft.aulast=Cahill&rft.aufirst=D.+P.&rft.au=Kinzler%2C+K.+W.&rft.au=Vogelstein%2C+B.&rft.au=Lengauer%2C+C.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-21"><span class="mw-cite-backlink"><b><a href="#cite_ref-21">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHuiZhenHuiZhongBaoFu2015" class="citation cs2">Hui, T.; Zhen, G.; HuiZhong, L.; BaoFu, Z.; Gang, W.; Qing, Z.; DongSheng, P.; JunNian, Z. (2015), "DNA damage response – A double-edged sword in cancer prevention and cancer therapy", <i>Cancer Letters</i>, <b>358</b> (1): 8–16, <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.canlet.2014.12.038">10.1016/j.canlet.2014.12.038</a>, <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/25528631">25528631</a></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Cancer+Letters&rft.atitle=DNA+damage+response+%E2%80%93+A+double-edged+sword+in+cancer+prevention+and+cancer+therapy&rft.volume=358&rft.issue=1&rft.pages=8-16&rft.date=2015&rft_id=info%3Adoi%2F10.1016%2Fj.canlet.2014.12.038&rft_id=info%3Apmid%2F25528631&rft.aulast=Hui&rft.aufirst=T.&rft.au=Zhen%2C+G.&rft.au=HuiZhong%2C+L.&rft.au=BaoFu%2C+Z.&rft.au=Gang%2C+W.&rft.au=Qing%2C+Z.&rft.au=DongSheng%2C+P.&rft.au=JunNian%2C+Z.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-pmid11237011-22"><span class="mw-cite-backlink"><b><a href="#cite_ref-pmid11237011_22-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFLander_ESLinton_LMBirren_BNusbaum_C2001" class="citation journal cs1">Lander ES; Linton LM; Birren B; Nusbaum C; Zody MC; Baldwin J; Devon K; Dewar K; Doyle M; FitzHugh W; et al. (February 2001). <a rel="nofollow" class="external text" href="https://deepblue.lib.umich.edu/bitstream/2027.42/62798/1/409860a0.pdf">"Initial sequencing and analysis of the human genome"</a> <span class="cs1-format">(PDF)</span>. <i>Nature</i>. <b>409</b> (6822): 860–921. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2001Natur.409..860L">2001Natur.409..860L</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1038%2F35057062">10.1038/35057062</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/11237011">11237011</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Initial+sequencing+and+analysis+of+the+human+genome&rft.volume=409&rft.issue=6822&rft.pages=860-921&rft.date=2001-02&rft_id=info%3Apmid%2F11237011&rft_id=info%3Adoi%2F10.1038%2F35057062&rft_id=info%3Abibcode%2F2001Natur.409..860L&rft.au=Lander+ES&rft.au=Linton+LM&rft.au=Birren+B&rft.au=Nusbaum+C&rft.au=Zody+MC&rft.au=Baldwin+J&rft.au=Devon+K&rft.au=Dewar+K&rft.au=Doyle+M&rft.au=FitzHugh+W&rft_id=https%3A%2F%2Fdeepblue.lib.umich.edu%2Fbitstream%2F2027.42%2F62798%2F1%2F409860a0.pdf&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-23"><span class="mw-cite-backlink"><b><a href="#cite_ref-23">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRoach_JCGlusman_GSmit_AF2010" class="citation journal cs1">Roach JC; Glusman G; Smit AF; et al. (April 2010). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037280">"Analysis of genetic inheritance in a family quartet by whole-genome sequencing"</a>. <i>Science</i>. <b>328</b> (5978): 636–9. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2010Sci...328..636R">2010Sci...328..636R</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1126%2Fscience.1186802">10.1126/science.1186802</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037280">3037280</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/20220176">20220176</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Science&rft.atitle=Analysis+of+genetic+inheritance+in+a+family+quartet+by+whole-genome+sequencing&rft.volume=328&rft.issue=5978&rft.pages=636-9&rft.date=2010-04&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3037280%23id-name%3DPMC&rft_id=info%3Apmid%2F20220176&rft_id=info%3Adoi%2F10.1126%2Fscience.1186802&rft_id=info%3Abibcode%2F2010Sci...328..636R&rft.au=Roach+JC&rft.au=Glusman+G&rft.au=Smit+AF&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3037280&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-24"><span class="mw-cite-backlink"><b><a href="#cite_ref-24">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCampbell_CDChong_JXMalig_M2012" class="citation journal cs1">Campbell CD; Chong JX; Malig M; et al. (November 2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483378">"Estimating the human mutation rate using autozygosity in a founder population"</a>. <i>Nat. Genet</i>. <b>44</b> (11): 1277–81. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fng.2418">10.1038/ng.2418</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483378">3483378</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23001126">23001126</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nat.+Genet.&rft.atitle=Estimating+the+human+mutation+rate+using+autozygosity+in+a+founder+population&rft.volume=44&rft.issue=11&rft.pages=1277-81&rft.date=2012-11&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3483378%23id-name%3DPMC&rft_id=info%3Apmid%2F23001126&rft_id=info%3Adoi%2F10.1038%2Fng.2418&rft.au=Campbell+CD&rft.au=Chong+JX&rft.au=Malig+M&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3483378&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-25"><span class="mw-cite-backlink"><b><a href="#cite_ref-25">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCunninghamFiebelkornJohnsonMeredith2011" class="citation journal cs1">Cunningham, FH; Fiebelkorn, S; Johnson, M; Meredith, C (2011). "A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants". <i>Food Chem Toxicol</i>. <b>49</b> (11): 2921–2933. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.fct.2011.07.019">10.1016/j.fct.2011.07.019</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21802474">21802474</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Food+Chem+Toxicol&rft.atitle=A+novel+application+of+the+Margin+of+Exposure+approach%3A+segregation+of+tobacco+smoke+toxicants&rft.volume=49&rft.issue=11&rft.pages=2921-2933&rft.date=2011&rft_id=info%3Adoi%2F10.1016%2Fj.fct.2011.07.019&rft_id=info%3Apmid%2F21802474&rft.aulast=Cunningham&rft.aufirst=FH&rft.au=Fiebelkorn%2C+S&rft.au=Johnson%2C+M&rft.au=Meredith%2C+C&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-26"><span class="mw-cite-backlink"><b><a href="#cite_ref-26">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCuozzoPorcelliniAngrisanoMorano2007" class="citation journal cs1">Cuozzo, C; Porcellini, A; Angrisano, T; Morano, A; Lee, B; Di Pardo, A; Messina, S; Iuliano, R; Fusco, A; Santillo, MR; Muller, MT; Chiariotti, L; Gottesman, ME; Avvedimento, EV (2007). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1913100">"DNA damage, homology-directed repair, and DNA methylation"</a>. <i>PLOS Genet</i>. <b>3</b> (7): e110. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1371%2Fjournal.pgen.0030110">10.1371/journal.pgen.0030110</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1913100">1913100</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17616978">17616978</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=PLOS+Genet&rft.atitle=DNA+damage%2C+homology-directed+repair%2C+and+DNA+methylation&rft.volume=3&rft.issue=7&rft.pages=e110&rft.date=2007&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1913100%23id-name%3DPMC&rft_id=info%3Apmid%2F17616978&rft_id=info%3Adoi%2F10.1371%2Fjournal.pgen.0030110&rft.aulast=Cuozzo&rft.aufirst=C&rft.au=Porcellini%2C+A&rft.au=Angrisano%2C+T&rft.au=Morano%2C+A&rft.au=Lee%2C+B&rft.au=Di+Pardo%2C+A&rft.au=Messina%2C+S&rft.au=Iuliano%2C+R&rft.au=Fusco%2C+A&rft.au=Santillo%2C+MR&rft.au=Muller%2C+MT&rft.au=Chiariotti%2C+L&rft.au=Gottesman%2C+ME&rft.au=Avvedimento%2C+EV&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1913100&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-27"><span class="mw-cite-backlink"><b><a href="#cite_ref-27">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFO'HaganMohammadBaylin2008" class="citation journal cs1">O'Hagan, HM; Mohammad, HP; Baylin, SB (2008). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2491723">"Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island"</a>. <i>PLOS Genet</i>. <b>4</b> (8): e1000155. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1371%2Fjournal.pgen.1000155">10.1371/journal.pgen.1000155</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2491723">2491723</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/18704159">18704159</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=PLOS+Genet&rft.atitle=Double+strand+breaks+can+initiate+gene+silencing+and+SIRT1-dependent+onset+of+DNA+methylation+in+an+exogenous+promoter+CpG+island&rft.volume=4&rft.issue=8&rft.pages=e1000155&rft.date=2008&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2491723%23id-name%3DPMC&rft_id=info%3Apmid%2F18704159&rft_id=info%3Adoi%2F10.1371%2Fjournal.pgen.1000155&rft.aulast=O%27Hagan&rft.aufirst=HM&rft.au=Mohammad%2C+HP&rft.au=Baylin%2C+SB&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2491723&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-28"><span class="mw-cite-backlink"><b><a href="#cite_ref-28">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGottschalkTiminszkyKongJin2009" class="citation journal cs1">Gottschalk, AJ; Timinszky, G; Kong, SE; Jin, J; Cai, Y; Swanson, SK; Washburn, MP; Florens, L; Ladurner, AG; Conaway, JW; Conaway, RC (2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722505">"Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler"</a>. <i>Proc Natl Acad Sci U S A</i>. <b>106</b> (33): 13770–4. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2009PNAS..10613770G">2009PNAS..10613770G</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1073%2Fpnas.0906920106">10.1073/pnas.0906920106</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722505">2722505</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19666485">19666485</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Proc+Natl+Acad+Sci+U+S+A&rft.atitle=Poly%28ADP-ribosyl%29ation+directs+recruitment+and+activation+of+an+ATP-dependent+chromatin+remodeler&rft.volume=106&rft.issue=33&rft.pages=13770-4&rft.date=2009&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2722505%23id-name%3DPMC&rft_id=info%3Apmid%2F19666485&rft_id=info%3Adoi%2F10.1073%2Fpnas.0906920106&rft_id=info%3Abibcode%2F2009PNAS..10613770G&rft.aulast=Gottschalk&rft.aufirst=AJ&rft.au=Timinszky%2C+G&rft.au=Kong%2C+SE&rft.au=Jin%2C+J&rft.au=Cai%2C+Y&rft.au=Swanson%2C+SK&rft.au=Washburn%2C+MP&rft.au=Florens%2C+L&rft.au=Ladurner%2C+AG&rft.au=Conaway%2C+JW&rft.au=Conaway%2C+RC&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2722505&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-pmid22492626-29"><span class="mw-cite-backlink"><b><a href="#cite_ref-pmid22492626_29-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFYost_SESmith_ENSchwab_RBBao_L2012" class="citation journal cs1">Yost SE; Smith EN; Schwab RB; Bao L; Jung H; Wang X; Voest E; Pierce JP; Messer K; Parker BA; Harismendy O; Frazer KA (August 2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413110">"Identification of high-confidence somatic mutations in whole genome sequence of formalin-fixed breast cancer specimens"</a>. <i>Nucleic Acids Res</i>. <b>40</b> (14): e107. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1093%2Fnar%2Fgks299">10.1093/nar/gks299</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413110">3413110</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22492626">22492626</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nucleic+Acids+Res.&rft.atitle=Identification+of+high-confidence+somatic+mutations+in+whole+genome+sequence+of+formalin-fixed+breast+cancer+specimens&rft.volume=40&rft.issue=14&rft.pages=e107&rft.date=2012-08&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3413110%23id-name%3DPMC&rft_id=info%3Apmid%2F22492626&rft_id=info%3Adoi%2F10.1093%2Fnar%2Fgks299&rft.au=Yost+SE&rft.au=Smith+EN&rft.au=Schwab+RB&rft.au=Bao+L&rft.au=Jung+H&rft.au=Wang+X&rft.au=Voest+E&rft.au=Pierce+JP&rft.au=Messer+K&rft.au=Parker+BA&rft.au=Harismendy+O&rft.au=Frazer+KA&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3413110&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-pmid22622578-30"><span class="mw-cite-backlink"><b><a href="#cite_ref-pmid22622578_30-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBerger_MFHodis_EHeffernan_TPDeribe_YL2012" class="citation journal cs1">Berger MF; Hodis E; Heffernan TP; Deribe YL; Lawrence MS; Protopopov A; Ivanova E; Watson IR; Nickerson E; Ghosh P; Zhang H; Zeid R; Ren X; Cibulskis K; Sivachenko AY; Wagle N; Sucker A; Sougnez C; Onofrio R; Ambrogio L; Auclair D; Fennell T; Carter SL; Drier Y; Stojanov P; Singer MA; Voet D; Jing R; Saksena G; Barretina J; Ramos AH; Pugh TJ; Stransky N; Parkin M; Winckler W; Mahan S; Ardlie K; Baldwin J; Wargo J; Schadendorf D; Meyerson M; Gabriel SB; Golub TR; Wagner SN; Lander ES; Getz G; Chin L; Garraway LA (May 2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367798">"Melanoma genome sequencing reveals frequent PREX2 mutations"</a>. <i>Nature</i>. <b>485</b> (7399): 502–6. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2012Natur.485..502B">2012Natur.485..502B</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fnature11071">10.1038/nature11071</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367798">3367798</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22622578">22622578</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Melanoma+genome+sequencing+reveals+frequent+PREX2+mutations&rft.volume=485&rft.issue=7399&rft.pages=502-6&rft.date=2012-05&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3367798%23id-name%3DPMC&rft_id=info%3Apmid%2F22622578&rft_id=info%3Adoi%2F10.1038%2Fnature11071&rft_id=info%3Abibcode%2F2012Natur.485..502B&rft.au=Berger+MF&rft.au=Hodis+E&rft.au=Heffernan+TP&rft.au=Deribe+YL&rft.au=Lawrence+MS&rft.au=Protopopov+A&rft.au=Ivanova+E&rft.au=Watson+IR&rft.au=Nickerson+E&rft.au=Ghosh+P&rft.au=Zhang+H&rft.au=Zeid+R&rft.au=Ren+X&rft.au=Cibulskis+K&rft.au=Sivachenko+AY&rft.au=Wagle+N&rft.au=Sucker+A&rft.au=Sougnez+C&rft.au=Onofrio+R&rft.au=Ambrogio+L&rft.au=Auclair+D&rft.au=Fennell+T&rft.au=Carter+SL&rft.au=Drier+Y&rft.au=Stojanov+P&rft.au=Singer+MA&rft.au=Voet+D&rft.au=Jing+R&rft.au=Saksena+G&rft.au=Barretina+J&rft.au=Ramos+AH&rft.au=Pugh+TJ&rft.au=Stransky+N&rft.au=Parkin+M&rft.au=Winckler+W&rft.au=Mahan+S&rft.au=Ardlie+K&rft.au=Baldwin+J&rft.au=Wargo+J&rft.au=Schadendorf+D&rft.au=Meyerson+M&rft.au=Gabriel+SB&rft.au=Golub+TR&rft.au=Wagner+SN&rft.au=Lander+ES&rft.au=Getz+G&rft.au=Chin+L&rft.au=Garraway+LA&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3367798&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-Narayanan-31"><span class="mw-cite-backlink"><b><a href="#cite_ref-Narayanan_31-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFNarayanan_LFritzell_JABaker_SMLiskay_RM1997" class="citation journal cs1">Narayanan L; Fritzell JA; Baker SM; Liskay RM; Glazer PM (April 1997). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20332">"Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. <b>94</b> (7): 3122–7. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/1997PNAS...94.3122N">1997PNAS...94.3122N</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1073%2Fpnas.94.7.3122">10.1073/pnas.94.7.3122</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20332">20332</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/9096356">9096356</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Proc.+Natl.+Acad.+Sci.+U.S.A.&rft.atitle=Elevated+levels+of+mutation+in+multiple+tissues+of+mice+deficient+in+the+DNA+mismatch+repair+gene+Pms2&rft.volume=94&rft.issue=7&rft.pages=3122-7&rft.date=1997-04&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC20332%23id-name%3DPMC&rft_id=info%3Apmid%2F9096356&rft_id=info%3Adoi%2F10.1073%2Fpnas.94.7.3122&rft_id=info%3Abibcode%2F1997PNAS...94.3122N&rft.au=Narayanan+L&rft.au=Fritzell+JA&rft.au=Baker+SM&rft.au=Liskay+RM&rft.au=Glazer+PM&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC20332&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-Hegan-32"><span class="mw-cite-backlink"><b><a href="#cite_ref-Hegan_32-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHegan_DCNarayanan_LJirik_FREdelmann_W2006" class="citation journal cs1">Hegan DC; Narayanan L; Jirik FR; Edelmann W; Liskay RM; Glazer PM (December 2006). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612936">"Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6"</a>. <i>Carcinogenesis</i>. <b>27</b> (12): 2402–8. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1093%2Fcarcin%2Fbgl079">10.1093/carcin/bgl079</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612936">2612936</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16728433">16728433</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Differing+patterns+of+genetic+instability+in+mice+deficient+in+the+mismatch+repair+genes+Pms2%2C+Mlh1%2C+Msh2%2C+Msh3+and+Msh6&rft.volume=27&rft.issue=12&rft.pages=2402-8&rft.date=2006-12&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2612936%23id-name%3DPMC&rft_id=info%3Apmid%2F16728433&rft_id=info%3Adoi%2F10.1093%2Fcarcin%2Fbgl079&rft.au=Hegan+DC&rft.au=Narayanan+L&rft.au=Jirik+FR&rft.au=Edelmann+W&rft.au=Liskay+RM&rft.au=Glazer+PM&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2612936&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-Tutt-33"><span class="mw-cite-backlink"><b><a href="#cite_ref-Tutt_33-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFTutt_ANvan_Oostrom_CTRoss_GMvan_Steeg_H2002" class="citation journal cs1">Tutt AN; van Oostrom CT; Ross GM; van Steeg H; Ashworth A (March 2002). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1084010">"Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation"</a>. <i>EMBO Rep</i>. <b>3</b> (3): 255–60. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1093%2Fembo-reports%2Fkvf037">10.1093/embo-reports/kvf037</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1084010">1084010</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/11850397">11850397</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=EMBO+Rep.&rft.atitle=Disruption+of+Brca2+increases+the+spontaneous+mutation+rate+in+vivo%3A+synergism+with+ionizing+radiation&rft.volume=3&rft.issue=3&rft.pages=255-60&rft.date=2002-03&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1084010%23id-name%3DPMC&rft_id=info%3Apmid%2F11850397&rft_id=info%3Adoi%2F10.1093%2Fembo-reports%2Fkvf037&rft.au=Tutt+AN&rft.au=van+Oostrom+CT&rft.au=Ross+GM&rft.au=van+Steeg+H&rft.au=Ashworth+A&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1084010&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-34"><span class="mw-cite-backlink"><b><a href="#cite_ref-34">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGerman1969" class="citation journal cs1">German, J (Mar 1969). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1706430">"Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients"</a>. <i>Am J Hum Genet</i>. <b>21</b> (2): 196–227. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1706430">1706430</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/5770175">5770175</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Am+J+Hum+Genet&rft.atitle=Bloom%27s+syndrome.+I.+Genetical+and+clinical+observations+in+the+first+twenty-seven+patients&rft.volume=21&rft.issue=2&rft.pages=196-227&rft.date=1969-03&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1706430%23id-name%3DPMC&rft_id=info%3Apmid%2F5770175&rft.aulast=German&rft.aufirst=J&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1706430&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-pmid15888787-35"><span class="mw-cite-backlink"><b><a href="#cite_ref-pmid15888787_35-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHalford_SRowan_ASawyer_ETalbot_I2005" class="citation journal cs1">Halford S; Rowan A; Sawyer E; Talbot I; Tomlinson I (June 2005). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774551">"O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions"</a>. <i>Gut</i>. <b>54</b> (6): 797–802. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1136%2Fgut.2004.059535">10.1136/gut.2004.059535</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774551">1774551</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/15888787">15888787</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Gut&rft.atitle=O%286%29-methylguanine+methyltransferase+in+colorectal+cancers%3A+detection+of+mutations%2C+loss+of+expression%2C+and+weak+association+with+G%3AC%3EA%3AT+transitions&rft.volume=54&rft.issue=6&rft.pages=797-802&rft.date=2005-06&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1774551%23id-name%3DPMC&rft_id=info%3Apmid%2F15888787&rft_id=info%3Adoi%2F10.1136%2Fgut.2004.059535&rft.au=Halford+S&rft.au=Rowan+A&rft.au=Sawyer+E&rft.au=Talbot+I&rft.au=Tomlinson+I&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1774551&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-36"><span class="mw-cite-backlink"><b><a href="#cite_ref-36">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFTruningerMenigattiLuzRussell2005" class="citation journal cs1">Truninger, K; Menigatti, M; Luz, J; Russell, A; Haider, R; Gebbers, JO; Bannwart, F; Yurtsever, H; Neuweiler, J; Riehle, HM; Cattaruzza, MS; Heinimann, K; Schär, P; Jiricny, J; Marra, G (2005). <a rel="nofollow" class="external text" href="https://doi.org/10.1053%2Fj.gastro.2005.01.056">"Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer"</a>. <i>Gastroenterology</i>. <b>128</b> (5): 1160–1171. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1053%2Fj.gastro.2005.01.056">10.1053/j.gastro.2005.01.056</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/15887099">15887099</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=Immunohistochemical+analysis+reveals+high+frequency+of+PMS2+defects+in+colorectal+cancer&rft.volume=128&rft.issue=5&rft.pages=1160-1171&rft.date=2005&rft_id=info%3Adoi%2F10.1053%2Fj.gastro.2005.01.056&rft_id=info%3Apmid%2F15887099&rft.aulast=Truninger&rft.aufirst=K&rft.au=Menigatti%2C+M&rft.au=Luz%2C+J&rft.au=Russell%2C+A&rft.au=Haider%2C+R&rft.au=Gebbers%2C+JO&rft.au=Bannwart%2C+F&rft.au=Yurtsever%2C+H&rft.au=Neuweiler%2C+J&rft.au=Riehle%2C+HM&rft.au=Cattaruzza%2C+MS&rft.au=Heinimann%2C+K&rft.au=Sch%C3%A4r%2C+P&rft.au=Jiricny%2C+J&rft.au=Marra%2C+G&rft_id=https%3A%2F%2Fdoi.org%2F10.1053%252Fj.gastro.2005.01.056&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-37"><span class="mw-cite-backlink"><b><a href="#cite_ref-37">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFValeriGaspariniFabbriBraconi2010" class="citation journal cs1">Valeri, N; Gasparini, P; Fabbri, M; Braconi, C; Veronese, A; Lovat, F; Adair, B; Vannini, I; Fanini, F; Bottoni, A; Costinean, S; Sandhu, SK; Nuovo, GJ; Alder, H; Gafa, R; Calore, F; Ferracin, M; Lanza, G; Volinia, S; Negrini, M; Mcllhatton, MA; Amadori, D; Fishel, R; Croce, CM (2010). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872463">"Modulation of mismatch repair and genomic stability by miR-155"</a>. <i>Proc Natl Acad Sci USA</i>. <b>107</b> (15): 6982–6987. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2010PNAS..107.6982V">2010PNAS..107.6982V</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1073%2Fpnas.1002472107">10.1073/pnas.1002472107</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872463">2872463</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/20351277">20351277</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Proc+Natl+Acad+Sci+USA&rft.atitle=Modulation+of+mismatch+repair+and+genomic+stability+by+miR-155&rft.volume=107&rft.issue=15&rft.pages=6982-6987&rft.date=2010&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2872463%23id-name%3DPMC&rft_id=info%3Apmid%2F20351277&rft_id=info%3Adoi%2F10.1073%2Fpnas.1002472107&rft_id=info%3Abibcode%2F2010PNAS..107.6982V&rft.aulast=Valeri&rft.aufirst=N&rft.au=Gasparini%2C+P&rft.au=Fabbri%2C+M&rft.au=Braconi%2C+C&rft.au=Veronese%2C+A&rft.au=Lovat%2C+F&rft.au=Adair%2C+B&rft.au=Vannini%2C+I&rft.au=Fanini%2C+F&rft.au=Bottoni%2C+A&rft.au=Costinean%2C+S&rft.au=Sandhu%2C+SK&rft.au=Nuovo%2C+GJ&rft.au=Alder%2C+H&rft.au=Gafa%2C+R&rft.au=Calore%2C+F&rft.au=Ferracin%2C+M&rft.au=Lanza%2C+G&rft.au=Volinia%2C+S&rft.au=Negrini%2C+M&rft.au=Mcllhatton%2C+MA&rft.au=Amadori%2C+D&rft.au=Fishel%2C+R&rft.au=Croce%2C+CM&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2872463&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-38"><span class="mw-cite-backlink"><b><a href="#cite_ref-38">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFFacistaNguyenLewisPrasad2012" class="citation journal cs1">Facista, A; Nguyen, H; Lewis, C; Prasad, AR; Ramsey, L; Zaitlin, B; Nfonsam, V; Krouse, RS; Bernstein, H; Payne, CM; Stern, S; Oatman, N; Banerjee, B; Bernstein, C (2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351028">"Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer"</a>. <i>Genome Integr</i>. <b>3</b> (1): 3. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1186%2F2041-9414-3-3">10.1186/2041-9414-3-3</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351028">3351028</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22494821">22494821</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Genome+Integr&rft.atitle=Deficient+expression+of+DNA+repair+enzymes+in+early+progression+to+sporadic+colon+cancer&rft.volume=3&rft.issue=1&rft.pages=3&rft.date=2012&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3351028%23id-name%3DPMC&rft_id=info%3Apmid%2F22494821&rft_id=info%3Adoi%2F10.1186%2F2041-9414-3-3&rft.aulast=Facista&rft.aufirst=A&rft.au=Nguyen%2C+H&rft.au=Lewis%2C+C&rft.au=Prasad%2C+AR&rft.au=Ramsey%2C+L&rft.au=Zaitlin%2C+B&rft.au=Nfonsam%2C+V&rft.au=Krouse%2C+RS&rft.au=Bernstein%2C+H&rft.au=Payne%2C+CM&rft.au=Stern%2C+S&rft.au=Oatman%2C+N&rft.au=Banerjee%2C+B&rft.au=Bernstein%2C+C&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3351028&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-39"><span class="mw-cite-backlink"><b><a href="#cite_ref-39">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFZheng2013" class="citation journal cs1">Zheng, Jie (Nov 2013). <a rel="nofollow" class="external text" href="https://doi.org/10.3892%2For.2013.2677">"Oncogenic chromosomal translocations and human cancer (Review)"</a>. <i>Oncology Reports</i>. <b>30</b> (5): 2011–2019. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.3892%2For.2013.2677">10.3892/or.2013.2677</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23970180">23970180</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Oncology+Reports&rft.atitle=Oncogenic+chromosomal+translocations+and+human+cancer+%28Review%29&rft.volume=30&rft.issue=5&rft.pages=2011-2019&rft.date=2013-11&rft_id=info%3Adoi%2F10.3892%2For.2013.2677&rft_id=info%3Apmid%2F23970180&rft.aulast=Zheng&rft.aufirst=Jie&rft_id=https%3A%2F%2Fdoi.org%2F10.3892%252For.2013.2677&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> <li id="cite_note-40"><span class="mw-cite-backlink"><b><a href="#cite_ref-40">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRamiroSan-MarinMcBrideJankovic2007" class="citation book cs1">Ramiro, Almudena; San-Marin, Bernardo Reina; McBride, Kevin; Jankovic, Mila; Barreto, Vasco; Nussenzweig, Andre; Nussenzweig, Michel C. (2007). <i>Advances in Immunology</i>. Elsevier. pp. 75–107. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-12-373706-9" title="Special:BookSources/978-0-12-373706-9"><bdi>978-0-12-373706-9</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Advances+in+Immunology&rft.pages=75-107&rft.pub=Elsevier&rft.date=2007&rft.isbn=978-0-12-373706-9&rft.aulast=Ramiro&rft.aufirst=Almudena&rft.au=San-Marin%2C+Bernardo+Reina&rft.au=McBride%2C+Kevin&rft.au=Jankovic%2C+Mila&rft.au=Barreto%2C+Vasco&rft.au=Nussenzweig%2C+Andre&rft.au=Nussenzweig%2C+Michel+C.&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGenome+instability" class="Z3988"></span></span> </li> </ol></div> <style data-mw-deduplicate="TemplateStyles:r1130092004">.mw-parser-output .portal-bar{font-size:88%;font-weight:bold;display:flex;justify-content:center;align-items:baseline}.mw-parser-output .portal-bar-bordered{padding:0 2em;background-color:#fdfdfd;border:1px solid #a2a9b1;clear:both;margin:1em auto 0}.mw-parser-output .portal-bar-related{font-size:100%;justify-content:flex-start}.mw-parser-output .portal-bar-unbordered{padding:0 1.7em;margin-left:0}.mw-parser-output .portal-bar-header{margin:0 1em 0 0.5em;flex:0 0 auto;min-height:24px}.mw-parser-output .portal-bar-content{display:flex;flex-flow:row wrap;flex:0 1 auto;padding:0.15em 0;column-gap:1em;align-items:baseline;margin:0;list-style:none}.mw-parser-output .portal-bar-content-related{margin:0;list-style:none}.mw-parser-output .portal-bar-item{display:inline-block;margin:0.15em 0.2em;min-height:24px;line-height:24px}@media screen and (max-width:768px){.mw-parser-output .portal-bar{font-size:88%;font-weight:bold;display:flex;flex-flow:column wrap;align-items:baseline}.mw-parser-output .portal-bar-header{text-align:center;flex:0;padding-left:0.5em;margin:0 auto}.mw-parser-output .portal-bar-related{font-size:100%;align-items:flex-start}.mw-parser-output .portal-bar-content{display:flex;flex-flow:row wrap;align-items:center;flex:0;column-gap:1em;border-top:1px solid #a2a9b1;margin:0 auto;list-style:none}.mw-parser-output .portal-bar-content-related{border-top:none;margin:0;list-style:none}}.mw-parser-output .navbox+link+.portal-bar,.mw-parser-output .navbox+style+.portal-bar,.mw-parser-output .navbox+link+.portal-bar-bordered,.mw-parser-output .navbox+style+.portal-bar-bordered,.mw-parser-output .sister-bar+link+.portal-bar,.mw-parser-output .sister-bar+style+.portal-bar,.mw-parser-output .portal-bar+.navbox-styles+.navbox,.mw-parser-output .portal-bar+.navbox-styles+.sister-bar{margin-top:-1px}</style><div class="portal-bar noprint metadata noviewer portal-bar-bordered" role="navigation" aria-label="Portals"><span class="portal-bar-header"><a href="/wiki/Wikipedia:Contents/Portals" title="Wikipedia:Contents/Portals">Portals</a>:</span><ul class="portal-bar-content"><li class="portal-bar-item"><span class="nowrap"><span typeof="mw:File"><a href="/wiki/File:Issoria_lathonia.jpg" class="mw-file-description"><img alt="icon" src="//upload.wikimedia.org/wikipedia/commons/thumb/2/2d/Issoria_lathonia.jpg/21px-Issoria_lathonia.jpg" decoding="async" width="21" height="15" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/2/2d/Issoria_lathonia.jpg/32px-Issoria_lathonia.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/2/2d/Issoria_lathonia.jpg/42px-Issoria_lathonia.jpg 2x" data-file-width="629" data-file-height="445" /></a></span> </span><a href="/wiki/Portal:Biology" title="Portal:Biology">Biology</a></li><li class="portal-bar-item"><span class="nowrap"><span typeof="mw:File"><span><img alt="icon" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/WHO_Rod.svg/8px-WHO_Rod.svg.png" decoding="async" width="8" height="19" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/WHO_Rod.svg/12px-WHO_Rod.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d6/WHO_Rod.svg/16px-WHO_Rod.svg.png 2x" data-file-width="107" data-file-height="250" /></span></span> </span><a href="/wiki/Portal:Medicine" title="Portal:Medicine">Medicine</a></li></ul></div>    </div><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?type=1x1" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" href="https://en.wikipedia.org/w/index.php?title=Genome_instability&oldid=1238604012">https://en.wikipedia.org/w/index.php?title=Genome_instability&oldid=1238604012</a>"</div></div> <div id="catlinks" class="catlinks" data-mw="interface"><div id="mw-normal-catlinks" class="mw-normal-catlinks"><a href="/wiki/Help:Category" title="Help:Category">Categories</a>: <ul><li><a href="/wiki/Category:Chromosomes" title="Category:Chromosomes">Chromosomes</a></li><li><a href="/wiki/Category:Cancer" title="Category:Cancer">Cancer</a></li><li><a href="/wiki/Category:Mutation" title="Category:Mutation">Mutation</a></li></ul></div><div id="mw-hidden-catlinks" class="mw-hidden-catlinks mw-hidden-cats-hidden">Hidden categories: <ul><li><a href="/wiki/Category:Articles_with_short_description" title="Category:Articles with short description">Articles with short description</a></li><li><a href="/wiki/Category:Short_description_matches_Wikidata" title="Category:Short description matches Wikidata">Short description matches Wikidata</a></li><li><a href="/wiki/Category:All_articles_with_unsourced_statements" title="Category:All articles with unsourced statements">All articles with unsourced statements</a></li><li><a href="/wiki/Category:Articles_with_unsourced_statements_from_February_2024" title="Category:Articles with unsourced statements from February 2024">Articles with unsourced statements from February 2024</a></li><li><a href="/wiki/Category:Articles_with_unsourced_statements_from_December_2019" title="Category:Articles with unsourced statements from December 2019">Articles with unsourced statements from December 2019</a></li></ul></div></div> </div> </main> </div> <div class="mw-footer-container"> <footer id="footer" class="mw-footer" > <ul id="footer-info"> <li id="footer-info-lastmod"> This page was last edited on 4 August 2024, at 18:55<span class="anonymous-show"> (UTC)</span>.</li> <li id="footer-info-copyright">Text is available under the <a href="/wiki/Wikipedia:Text_of_the_Creative_Commons_Attribution-ShareAlike_4.0_International_License" title="Wikipedia:Text of the Creative Commons Attribution-ShareAlike 4.0 International License">Creative Commons Attribution-ShareAlike 4.0 License</a>; additional terms may apply. By using this site, you agree to the <a href="https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Terms_of_Use" class="extiw" title="foundation:Special:MyLanguage/Policy:Terms of Use">Terms of Use</a> and <a href="https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Privacy_policy" class="extiw" title="foundation:Special:MyLanguage/Policy:Privacy policy">Privacy Policy</a>. Wikipedia® is a registered trademark of the <a rel="nofollow" class="external text" href="https://wikimediafoundation.org/">Wikimedia Foundation, Inc.</a>, a non-profit organization.</li> </ul> <ul id="footer-places"> <li id="footer-places-privacy"><a href="https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Privacy_policy">Privacy policy</a></li> <li id="footer-places-about"><a href="/wiki/Wikipedia:About">About Wikipedia</a></li> <li id="footer-places-disclaimers"><a href="/wiki/Wikipedia:General_disclaimer">Disclaimers</a></li> <li id="footer-places-contact"><a href="//en.wikipedia.org/wiki/Wikipedia:Contact_us">Contact Wikipedia</a></li> <li id="footer-places-wm-codeofconduct"><a href="https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Universal_Code_of_Conduct">Code of Conduct</a></li> <li id="footer-places-developers"><a href="https://developer.wikimedia.org">Developers</a></li> <li id="footer-places-statslink"><a href="https://stats.wikimedia.org/#/en.wikipedia.org">Statistics</a></li> <li id="footer-places-cookiestatement"><a href="https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Cookie_statement">Cookie statement</a></li> <li id="footer-places-mobileview"><a href="//en.m.wikipedia.org/w/index.php?title=Genome_instability&mobileaction=toggle_view_mobile" class="noprint stopMobileRedirectToggle">Mobile view</a></li> </ul> <ul id="footer-icons" class="noprint"> <li id="footer-copyrightico"><a href="https://wikimediafoundation.org/" class="cdx-button cdx-button--fake-button cdx-button--size-large cdx-button--fake-button--enabled"><img src="/static/images/footer/wikimedia-button.svg" width="84" height="29" alt="Wikimedia Foundation" loading="lazy"></a></li> <li id="footer-poweredbyico"><a href="https://www.mediawiki.org/" class="cdx-button cdx-button--fake-button cdx-button--size-large cdx-button--fake-button--enabled"><img src="/w/resources/assets/poweredby_mediawiki.svg" alt="Powered by MediaWiki" width="88" height="31" loading="lazy"></a></li> </ul> </footer> </div> </div> </div> <div class="vector-settings" id="p-dock-bottom"> <ul></ul> </div><script>(RLQ=window.RLQ||[]).push(function(){mw.config.set({"wgHostname":"mw-web.codfw.main-f69cdc8f6-4fxvw","wgBackendResponseTime":167,"wgPageParseReport":{"limitreport":{"cputime":"0.674","walltime":"0.760","ppvisitednodes":{"value":3933,"limit":1000000},"postexpandincludesize":{"value":125403,"limit":2097152},"templateargumentsize":{"value":3842,"limit":2097152},"expansiondepth":{"value":12,"limit":100},"expensivefunctioncount":{"value":7,"limit":500},"unstrip-depth":{"value":1,"limit":20},"unstrip-size":{"value":168921,"limit":5000000},"entityaccesscount":{"value":0,"limit":400},"timingprofile":["100.00% 679.841 1 -total"," 64.19% 436.363 1 Template:Reflist"," 49.95% 339.596 33 Template:Cite_journal"," 11.86% 80.658 1 Template:Short_description"," 9.72% 66.091 4 Template:Cn"," 8.77% 59.607 5 Template:Fix"," 7.04% 47.879 2 Template:Pagetype"," 5.38% 36.594 6 Template:Citation"," 4.91% 33.360 10 Template:Category_handler"," 4.56% 30.970 1 Template:Portal_bar"]},"scribunto":{"limitreport-timeusage":{"value":"0.450","limit":"10.000"},"limitreport-memusage":{"value":5954733,"limit":52428800}},"cachereport":{"origin":"mw-web.codfw.main-f69cdc8f6-v5bt4","timestamp":"20241122161626","ttl":2592000,"transientcontent":false}}});});</script> <script type="application/ld+json">{"@context":"https:\/\/schema.org","@type":"Article","name":"Genome instability","url":"https:\/\/en.wikipedia.org\/wiki\/Genome_instability","sameAs":"http:\/\/www.wikidata.org\/entity\/Q2892636","mainEntity":"http:\/\/www.wikidata.org\/entity\/Q2892636","author":{"@type":"Organization","name":"Contributors to Wikimedia projects"},"publisher":{"@type":"Organization","name":"Wikimedia Foundation, Inc.","logo":{"@type":"ImageObject","url":"https:\/\/www.wikimedia.org\/static\/images\/wmf-hor-googpub.png"}},"datePublished":"2011-08-10T21:29:04Z","dateModified":"2024-08-04T18:55:22Z","headline":"high frequency of mutations within the genome of a cellular lineage"}</script> </body> </html>