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Distinct roles for cyclins E and A during DNA replication complex assembly and activation

Coverley, D., Laman, H. and Laskey, R.A. (2002) Distinct roles for cyclins E and A during DNA replication complex assembly and activation. Nature Cell Biology, 4 (7). pp. 523-528. ISSN 1465-7392

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Initiation of DNA replication is regulated by cyclin-dependent protein kinase 2 (Cdk2) in association with two different regulatory subunits, cyclin A and cyclin E (reviewed in ref. 1). But why two different cyclins are required and why their order of activation is tightly regulated are unknown. Using a cell-free system for initiation of DNA replication that is based on G1 nuclei, G1 cytosol and recombinant proteins, we find that cyclins E and A have specialized roles during the transition from G0 to S phase. Cyclin E stimulates replication complex assembly by cooperating with Cdc6, to make G1 nuclei competent to replicate in vitro. Cyclin A has two separable functions: it activates DNA synthesis by replication complexes that are already assembled, and it inhibits the assembly of new complexes. Thus, cyclin E opens a 'window of opportunity' for replication complex assembly that is closed by cyclin A. The dual functions of cyclin A ensure that the assembly phase (G1) ends before DNA synthesis (S) begins, thereby preventing re-initiation until the next cell cycle.

Item Type: Article
Institution: The University of York
Academic Units: The University of York > Biology (York)
Depositing User: York RAE Import
Date Deposited: 20 Mar 2009 11:52
Last Modified: 20 Mar 2009 11:52
Published Version: http://dx.doi.org/10.1038/ncb813
Status: Published
Publisher: Nature Publishing Group
Identification Number: 10.1038/ncb813
URI: http://eprints.whiterose.ac.uk/id/eprint/7054

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