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Randell JC, et al.  (2006) Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol Cell 21(1):29-39

Abstract: Loading of the Mcm2-7 DNA replicative helicase onto origin-proximal DNA is a critical and tightly regulated event during the initiation of eukaryotic DNA replication. The resulting protein-DNA assembly is called the prereplicative complex (pre-RC), and its formation requires the origin recognition complex (ORC), Cdc6, Cdt1, and ATP. ATP hydrolysis by ORC is required for multiple rounds of Mcm2-7 loading. Here, we investigate the role of ATP hydrolysis by Cdc6 during pre-RC assembly. We find that Cdc6 is an ORC- and origin DNA-dependent ATPase that functions at a step preceding ATP hydrolysis by ORC. Inhibiting Cdc6 ATP hydrolysis stabilizes Cdt1 on origin DNA and prevents Mcm2-7 loading. In contrast, the initial association of Mcm2-7 with the other pre-RC components does not require ATP hydrolysis by Cdc6. Importantly, these coordinated yet distinct functions of ORC and Cdc6 ensure the correct temporal and spatial regulation of pre-RC formation.

Status: Published Type: Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't PubMed ID: 16387651

Topics addressed in this paper

Number of different genes curated to this paper: 13

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Topics Genes linked to topics (#1 - 10 )
CDC6 MCM2 MCM3 MCM4 MCM5 MCM6 MCM7 ORC1 ORC2 ORC3
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Topics Genes linked to topics (#11 - 13 )
ORC4 ORC5 TAH11
Alias blue ball
Function/Process blue ball
Primary Literature blue ball blue ball blue ball
Protein-Nucleic Acid Interactions blue ball blue ball blue ball
Regulation of blue ball
Regulatory Role blue ball blue ball
Substrates/Ligands/Cofactors blue ball blue ball
Techniques and Reagents blue ball blue ball blue ball

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