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| Regulation of early events in chromosome replication |
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| Author(s): Diffley JFX |
| Source: CURRENT BIOLOGY Volume: 14 Issue: 18 Pages: R778-R786 Published: SEP 21 2004 |
| Times Cited: 135 References: 126 |
| Abstract: Eukaryotic genomes are replicated from large numbers of replication origins distributed on multiple chromosomes. The activity of these origins must be coordinated so that the entire genome is efficiently and accurately replicated yet no region of the genome is ever replicated more than once. The past decade has seen significant advances in understanding how the initiation of DNA replication is regulated by key cell-cycle regulators, including the cyclin dependent kinases (CDKs) and the anaphase promoting complex/cyclosome (APC/C). The assembly of essential prereplicative complexes (pre-RCs) at origins only occurs when CDK activity is low and APC/C activity is high. Origin firing, however, can only occur when the APC/C is inactivated and CDKs become active. This two step mechanism ensures that no origin can fire more than once in a cell cycle. In all eukaryotes tested, CDKs can contribute to the inhibition of pre-RC assembly. This inhibition is characterised both by high degrees of redundancy and evolutionary plasticity. Geminin plays a crucial role in inhibiting licensing in metazoans and, like cyclins, is inactivated by the APC/C. Strategies involved in preventing re-replication in different organisms will be discussed. |
| Document Type: Review |
| Language: English |
| Reprint Address: Diffley, JFX (reprint author), Canc Res UK London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts England |
Addresses:
1. Canc Res UK London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts England |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 857BC |
| ISSN: 0960-9822 |
| DOI: 10.1016/j.cub.2004.09.019 |
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