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#Cdc6

2 public questions tagged with this topic.

What is the function of Cdc6 and Cdt1 in DNA replication?

Pre-replication complex formation establishes replication competence before S phase, separating helicase loading from activation. Origin recognition complex ORC marks replication origins throughout cell cycle at AT-rich sequences. In late mitosis and early G1 when CDK activity minimal due to APC/C-Cdh1 mediated cyclin degradation, AAA+ ATPase Cdc6 binds ORC and recruits chaperone Cdt1 bound to single hexamer of MCM2-7 helicase. ATP hydrolysis by Cdc6 and ORC opens MCM ring, allowing encirclement of double-stranded DNA and formation of inactive double hexamer encircling DNA in head-to-head orie

Ref: Bell & Labib, Genes & Dev 2016, Pre-RC Assembly. Alberts 7th ed., Chapter 5, Replication Licensing.

How does Cdc6 regulate DNA replication?

Origins are prepared for replication during G1 through hierarchical assembly of pre-replicative complex. Origin recognition complex remains bound to DNA throughout cell cycle serving as landing pad. ATPase Cdc6 then associates in G1 in ATP-bound form undergoing conformational change that stabilizes interaction with ORC and creates composite binding site for helicase chaperone complex comprising Cdt1 and MCM2-7 double hexamer. ATP hydrolysis by Cdc6 and ORC loads MCM rings encircling double-stranded DNA in head-to-head orientation for bidirectional replication. This licensed origin remains iner

Ref: Bell & Dutta, Origin Licensing by Cdc6 and MCM Loading, Annu Rev Biochem 2002; Alberts, Molecular Biology of the Cell, Chapter 5, DNA Replication Initiation.