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Global regulation of genome duplication in eukaryotes: an overview from the epifluorescence microscope

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Abstract

In eukaryotes, DNA replication is initiated along each chromosome at multiple sites called replication origins. Locally, each replication origin is “licensed” or specified at the end of the M and the beginning of the G1 phases of the cell cycle. During the S phase when DNA synthesis takes place, origins are activated in stages corresponding to early and late-replicating domains. The staged and progressive activation of replication origins reflects the need to maintain a strict balance between the number of active replication forks and the rate at which DNA synthesis proceeds. This suggests that origin densities (frequency of initiation) and replication fork movement (rates of elongation) must be coregulated to guarantee the efficient and complete duplication of each subchromosomal domain. Emerging evidence supports this proposal and suggests that the ATM/ATR intra-S phase checkpoint plays an important role in the coregulation of initiation frequencies and rates of elongation. In this paper, we review recent results concerning the mechanisms governing the global regulation of DNA replication and discuss the roles these mechanisms play in maintaining genome stability during both a normal and perturbed S phase.

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Acknowledgements

The authors would like to thank John Bechhoefer for the comments and careful reading of the manuscript, and Bianca Sclavi, Christophe Henry, Pierre Walrafen, Jean-Pascal Capp, and Jun Komatsu for the helpful discussions. The authors would also like to thank the three anonymous reviewers whose comments significantly improved the manuscript.

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  1. Genomic Vision, 29, rue Faubourg St. Jacques, Paris, 75014, France

    John Herrick & Aaron Bensimon

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  1. John Herrick
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  2. Aaron Bensimon
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Correspondence to John Herrick.

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Communicated by E.A. Nigg

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Herrick, J., Bensimon, A. Global regulation of genome duplication in eukaryotes: an overview from the epifluorescence microscope. Chromosoma 117, 243–260 (2008). https://doi.org/10.1007/s00412-007-0145-1

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  • DOI: https://doi.org/10.1007/s00412-007-0145-1

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