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Causes and consequences of replication stress

Nature Cell Biology volume 16, pages 2–9 (2014)Cite this article

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Abstract

Replication stress is a complex phenomenon that has serious implications for genome stability, cell survival and human disease. Generation of aberrant replication fork structures containing single-stranded DNA activates the replication stress response, primarily mediated by the kinase ATR (ATM- and Rad3-related). Along with its downstream effectors, ATR stabilizes and helps to restart stalled replication forks, avoiding the generation of DNA damage and genome instability. Understanding this response may be key to diagnosing and treating human diseases caused by defective responses to replication stress.

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Figure 1: Mechanisms of stalled replication fork restart and collapse.
Figure 2: Sources of replication stress.

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Acknowledgements

We would like to thank E. Brown, D. Cortez and members of the Cimprich and Pasero labs for thoughtful discussions and careful reading of this manuscript. We apologize to those whose excellent work could not be cited directly due to space limitations. Work in the K.A.C. laboratory is supported by the National Institutes of Health.

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  1. Michelle K. Zeman and Karlene A. Cimprich are in the Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA,

    Michelle K. Zeman & Karlene A. Cimprich

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Correspondence to Karlene A. Cimprich.

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Zeman, M., Cimprich, K. Causes and consequences of replication stress. Nat Cell Biol 16, 2–9 (2014). https://doi.org/10.1038/ncb2897

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