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DNA replication and homologous recombination factors: acting together to maintain genome stability

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Abstract

Genome duplication requires the coordinated action of multiple proteins to ensure a fast replication with high fidelity. These factors form a complex called the Replisome, which is assembled onto the DNA duplex to promote its unwinding and to catalyze the polymerization of two new strands. Key constituents of the Replisome are the Cdc45-Mcm2-7-GINS helicase and the And1-Claspin-Tipin-Tim1 complex, which coordinate DNA unwinding with polymerase alpha-, delta-, and epsilon- dependent DNA polymerization. These factors encounter numerous obstacles, such as endogenous DNA lesions leading to template breakage and complex structures arising from intrinsic features of specific DNA sequences. To overcome these roadblocks, homologous recombination DNA repair factors, such as Rad51 and the Mre11-Rad50-Nbs1 complex, are required to ensure complete and faithful replication. Consistent with this notion, many of the genes involved in this process result in lethal phenotypes when inactivated in organisms with complex and large genomes. Here, we summarize the architectural and functional properties of the Replisome and propose a unified view of DNA replication and repair processes.

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Acknowledgments

The authors should like to thank Adelina Davies for the critical reading of the manuscript. This work was funded by Cancer Research UK. V.C. is also supported by the European Research Council (ERC) start-up grant (206281), the Lister Institute of Preventive Medicine and the European Molecular Biology Organization (EMBO) Young Investigator Program (YIP).

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  1. Clare Hall Laboratories, London Research Institute, South Mimms, Herts, EN63LD, UK

    Antoine Aze, Jin Chuan Zhou, Alessandro Costa & Vincenzo Costanzo

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  1. Antoine Aze
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  2. Jin Chuan Zhou
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  3. Alessandro Costa
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  4. Vincenzo Costanzo
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Correspondence to Alessandro Costa or Vincenzo Costanzo.

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Aze, A., Zhou, J.C., Costa, A. et al. DNA replication and homologous recombination factors: acting together to maintain genome stability. Chromosoma 122, 401–413 (2013). https://doi.org/10.1007/s00412-013-0411-3

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  • DOI: https://doi.org/10.1007/s00412-013-0411-3

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