| | |  | | | | Record from Web of Science® | | | | | | |
| Distinct roles for cyclins E and A during DNA replication complex assembly and activation |
|
|
| Author(s): Coverley D, Laman H, Laskey RA |
| Source: NATURE CELL BIOLOGY Volume: 4 Issue: 7 Pages: 523-528 Published: JUL 2002 |
| Times Cited: 126 References: 32 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Coverley, D (reprint author), Hutchison MRC Res Ctr, Canc Cell Unit, Hills Rd, Cambridge CB2 2XZ, England |
Addresses:
1. Hutchison MRC Res Ctr, Canc Cell Unit, Cambridge CB2 2XZ, England
2. Univ York, Dept Biol, York YO10 5YW, N Yorkshire England
3. Canc Res UK, London WC2A 3PX, England |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Cell Biology |
| IDS Number: 568UL |
| ISSN: 1465-7392 |
| DOI: 10.1038/ncb813 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |