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5.05:_DNA_Replication
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<figure><img class="internal" alt="Diagram of DNA replication fork, showing template strands, leading and lagging strands, DNA polymerase, DNA ligase, and Okazaki fragments. Arrows indicate direction of replication." loading="lazy" src="https://bio.libretexts.org/@api/deki/files/6524/ReplicationFork.gif?revision=1" /><figcaption>Figure 5.5.3: Control of Replication</figcaption></figure> <p class="lt-bio-4743" style="background-color: unset;">With their multiple origins, how does the <strong>eukaryotic cell</strong> know which origins have been already replicated and which still await replication?</p> <p class="lt-bio-4743" style="background-color: unset;"><strong>An observation:</strong> When a cell in G<sub><font size="2">2</font></sub> of the cell cycle is fused with a cell in S phase, the DNA of the G<sub><font size="2">2</font></sub> nucleus does not begin replicating again even though replication is proceeding normally in the S-phase nucleus. Not until mitosis is completed, can freshly-synthesized DNA be replicated again.</p> <p class="lt-bio-4743" style="background-color: unset;">Two control mechanisms have been identified — one <strong>positive</strong> and one <strong>negative</strong>. This redundancy probably reflects the crucial importance of precise replication to the integrity of the genome.</p> <span id="Licensing:_positive_control_of_replication"></span><span id="Licensing:_positive_control_of_replication"></span><h2 style="background-color: unset;" class="lt-bio-4743">Licensing: positive control of replication</h2> <p class="lt-bio-4743" style="background-color: unset;">In order to be replicated, each origin of replication must be bound by:</p> <ul> <li class="lt-bio-4743" style="background-color: unset;">an <strong>O</strong>rigin <strong>R</strong>ecognition <strong>C</strong>omplex of proteins (<strong>ORC</strong>). These remain on the DNA throughout the process.</li> <li class="lt-bio-4743" style="background-color: unset;">Accessory proteins called <strong>licensing factors</strong>. These accumulate in the nucleus during G<sub><font size="2">1</font></sub> of the cell cycle. They include: <ul> <li class="lt-bio-4743" style="background-color: unset;">Cdc-6 and Cdt-1, which bind to the <strong>ORC</strong> and are essential for coating the DNA with</li> <li class="lt-bio-4743" style="background-color: unset;">MCM proteins. Only DNA coated with MCM proteins (there are 6 of them) can be replicated.</li> </ul> </li> </ul> <p class="lt-bio-4743" style="background-color: unset;">Once replication begins in S phase,</p> <ul> <li class="lt-bio-4743" style="background-color: unset;">Cdc-6 and Cdt-1 leave the ORCs (the latter by ubiquination and destruction in proteasomes).</li> <li class="lt-bio-4743" style="background-color: unset;">The MCM proteins leave in front of the advancing replication fork.</li> </ul> <footer class="mt-content-footer"> <style>/*<![CDATA[*/#mt-toc-container {display: none !important;}/*]]>*/</style><script type="text/javascript">/*<![CDATA[*/ $(function() { if(!window['autoDefinitionList']){ window['autoDefinitionList'] = true; $('dl').find('dt').on('click', function() { $(this).next().toggle('350'); }); } });/*]]>*/</script> <script defer="true" src="https://static.cloudflareinsights.com/beacon.min.js" data-cf-beacon="{"token": "483ec2414e274209a7e93c253192df0b"}"></script><script src="https://cdn.libretexts.net/github/LibreTextsMain/Miscellaneous/h5p-resizer.js"></script><script src="https://cdnjs.cloudflare.com/ajax/libs/iframe-resizer/4.2.11/iframeResizer.contentWindow.min.js" integrity="sha512-FOf4suFgz7OrWmBiyyWW48u/+6GaaAFSDHagh2EBu/GH/1+OQSYc0NFGeGeZK0gZ3vuU1ovmzVzD6bxmT4vayg==" crossorigin="anonymous"></script><script src="https://cdnjs.cloudflare.com/ajax/libs/iframe-resizer/4.2.11/iframeResizer.min.js" integrity="sha512-HY1lApSG7xxx8mYzs/lxRs+c5AaDThRaa3pvQB6puiswvf2lWqMJVf+8qSGiL4ZXfHQoPIqbd1TlpqfycPo3cQ==" crossorigin="anonymous"></script><script>/*<![CDATA[*/window.addEventListener('load', function(){$('iframe').iFrameResize({warningTimeout:0, scrolling: 'omit'});})/*]]>*/</script><script>/*<![CDATA[*/ window.PageNum = "auto"; window.InitialOffset = "false"; window.PageName = "5.5: DNA Replication"; /*]]>*/</script> <script type="text/javascript">/*<![CDATA[*/ // var front = window.PageNum.trim(); if(front=="auto"){ front = window.PageName.replace('\"', '\\\"').trim(); //front = "'..string.matchreplace(PageName,'\"','\\\"')..'".trim(); if(front.includes(":")){ front = front.split(":")[0].trim(); if(front.includes(".")){ front = front.split("."); front = front.map((int)=>int.includes("0")?parseInt(int,10):int).join("."); } front+="."; } else { front = ""; } } front = front.trim(); function loadMathJaxScript() { try { const script = document.createElement('script'); script.id = "mathjax-script"; script.src = "https://cdn.jsdelivr.net/npm/mathjax@4/tex-mml-svg.js"; script.type = "text/javascript"; script.defer = true; document.head.appendChild(script); } catch (err) { console.error(err); } } document.addEventListener('DOMContentLoaded', (e) => { loadMathJaxScript(); }); if (window.PageName !== 'Realtime MathJax'){ MathJax = { options: { ignoreHtmlClass: "tex2jax_ignore", processHtmlClass: "tex2jax_process", menuOptions: { settings: { zscale: "150%", zoom: "Double-Click", assistiveMml: true, // true to enable assitive MathML collapsible: false, // true to enable collapsible math }, }, }, output: { scale: 0.85, mtextInheritFont: false, displayOverflow: "linebreak", linebreaks: { width: "100%", }, }, startup: { pageReady: () => { if (window.activateBeeLine) { window.activateBeeLine(); } return MathJax.startup.defaultPageReady(); }, }, chtml: { matchFontHeight: true, }, tex: { tags: "all", tagformat: { number: (n) => { if (window.InitialOffset) { const offset = Number(window.InitialOffset); if(!offset) { return front + n; // If offset is falsy (nan, undefined, etc.) } const added = Number(n) + offset; return front + added; } else { return front + n; } }, }, macros: { eatSpaces: ['#1', 2, ['', ' ', '\\endSpaces']], PageIndex: ['{' + front.replace(/\./g, '{.}') + '\\eatSpaces#1 \\endSpaces}', 1], test: ["{" + front + "#1}", 1], mhchemrightleftharpoons: "{\\unicode{x21CC}\\,}", xrightleftharpoons: ['\\mhchemxrightleftharpoons[#1]{#2}', 2, ''] }, packages: { "[+]": [ "mhchem", "color", "cancel", "ams", "tagformat" ], }, }, loader: { '[tex]/mhchem': { ready() { const {MapHandler} = MathJax._.input.tex.MapHandler; const mhchem = MapHandler.getMap('mhchem-chars'); mhchem.lookup('mhchemrightarrow')._char = '\uE42D'; mhchem.lookup('mhchemleftarrow')._char = '\uE42C'; } }, load: [ "[tex]/mhchem", "[tex]/color", "[tex]/cancel", "[tex]/tagformat", ], }, }; }; ///*]]>*/</script> <hr class="autoattribution-divider" /><div class="autoattribution"><p>This page titled <a target="_blank" class="internal mt-self-link" href="/Sandboxes/johnnyphung/biology/05:_DNA/5.05:_DNA_Replication">5.5: DNA Replication</a> is shared under a <a rel="nofollow" href="https://creativecommons.org/licenses/by/3.0" target="_blank">CC BY 3.0</a> license and was authored, remixed, and/or curated by <a rel="nofollow" target="_blank" href="http://www.biology-pages.info/">John W. 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