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DNA replication stress: from molecular mechanisms to human disease

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Abstract

The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of “replicative stress” (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.

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Acknowledgments

We thank all members of the laboratory for useful discussions and apologize to the authors whose works are not cited due to space restrictions.

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  1. DNA Replication Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029, Madrid, Spain

    Sergio Muñoz & Juan Méndez

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  1. Sergio Muñoz
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Correspondence to Juan Méndez.

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This review article does not contain any studies with human participants or animals performed by any of the authors.

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The authors declare that they have no competing interests.

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Research in JM lab is supported by grants BFU2013-49153P and Consolider CSD2007-00015 from the Spanish Ministry of Economy and Competitiveness.

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Muñoz, S., Méndez, J. DNA replication stress: from molecular mechanisms to human disease. Chromosoma 126, 1–15 (2017). https://doi.org/10.1007/s00412-016-0573-x

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