M1 Fricker- Eukaryotic DNA replication

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Last updated 9:30 PM on 10/15/26
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4 Terms

1
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how does the pre-replicative complex form in eukaryotic DNA replication?

in late M/G1- licensing

  • the origin, a weakly bound A/T rich region is bound by the ORC initiator (origin recognition complex), creating enough torsional stress to separate the strands

  • Cdc6 and Cdt1 loaders combine with ORC and load each strand with an Mcm2-7 helicase (mini chromosome maintenance) by opening the hexamer ring

  • the helicases remain inactive until S phase


<p><strong>in late M/G1- licensing</strong></p><ul><li><p>the origin, a weakly bound <strong>A/T rich </strong>region is bound by the <strong>ORC initiator </strong>(origin recognition complex), creating enough<strong> torsional stress</strong> to separate the strands</p></li><li><p><strong>Cdc6 </strong>and <strong>Cdt1 loaders </strong>combine with ORC and load <strong>each </strong>strand with an <strong>Mcm2-7 helicase</strong> (mini chromosome maintenance) by opening the hexamer ring</p></li><li><p>the helicases remain <strong>inactive </strong>until <strong>S </strong>phase</p></li></ul><p></p>
2
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how is the pre-initiation complex formed and activated in eukaryotic DNA replication?

in late G1/S phase

  • the inactive pre-replicative complex (ORC, Cdc6, Cdt1 + 2 x MCM2-7 helicase) is activated to form the pre-initiation complex:

  • the CMG complex (Cdc45, MCM + GINS) is recruited to each MCM helicase, and acts as a docking site for inactive pol-epsilon on the leading strand

  • DDK and CDK (kinases) phosphorylate the MCMs and other binding proteins to activate the PIC


<p><strong>in late G1/S phase</strong></p><ul><li><p>the inactive<strong> pre-replicative complex</strong> (ORC, Cdc6, Cdt1 + 2 x MCM2-7 helicase) is activated to form the <strong>pre-initiation complex:</strong></p></li><li><p>the <strong>CMG </strong>complex (<strong>C</strong>dc45, <strong>M</strong>CM + <strong>G</strong>INS) is recruited to each MCM helicase, and acts as a docking site for inactive <strong>pol-epsilon </strong>on the <strong>leading </strong>strand</p></li><li><p><strong>DDK </strong>and <strong>CDK </strong>(kinases) <strong>phosphorylate </strong>the MCMs and other binding proteins to activate the PIC</p></li></ul><p></p>
3
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how is the replisome formed in eukaryotic DNA replication?

in late G1/S phase:

  • the inactive pre-initiation complex is converted into the replisome:

  • Ctf4 links pol-alpha to the CMG complex on the lagging strand


4
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why can eukaryotic DNA replication only occur once per cell cycle?

  • different kinases are present at different points in the cell cycle, which are involved in initiation

  • CDC-6 has to be replaced by CDC-45 to start

  • phosphorylation during activation triggers irreversible ubiquitination of proteins