Journal
FEBS LETTERS
Volume 586, Issue 18, Pages 2803-2812Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2012.07.042
Keywords
DNA replication; Licensing; Origin; S phase; Replisome
Funding
- Association for International Cancer Research
- European Research Council
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DNA replication is precisely regulated in time and space, thereby safeguarding genomic integrity. In eukaryotes, replication initiates from multiple sites along the genome, termed origins of replication, and propagates bidirectionally. Dynamic origin bound complexes dictate where and when replication should initiate. During late mitosis and G1 phase, putative origins are recognized and become licensed'' through the assembly of pre-replicative complexes (pre-RCs) that include the MCM2-7 helicases. Subsequently, at the G1/S phase transition, a fraction of pre-RCs are activated giving rise to the establishment of replication forks. Origin location is influenced by chromatin and nuclear organization and origin selection exhibits stochastic features. The regulatory mechanisms that govern these cell cycle events rely on the periodic fluctuation of cyclin dependent kinase (CDK) activity through the cell cycle. (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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