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
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.
|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|
|Publisher:||Nature Publishing Group|