Mol Cell. 2006 Jan 6;21(1):29-39.

Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase.

Randell JC, Bowers JL, Rodríguez HK, Bell SP.

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Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

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.

Comment in

Getting a grip on licensing: mechanism of stable Mcm2-7 loading onto replication origins. [Mol Cell. 2006]
Getting a grip on licensing: mechanism of stable Mcm2-7 loading onto replication origins.Cvetic CA, Walter JC. Mol Cell. 2006 Jan 20; 21(2):143-4.

PMID:: 16387651; [PubMed - indexed for MEDLINE]

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Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loading. [Genes Dev. 2007]
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Cited by 58 PubMed Central articles

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