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New insights into the mechanism of DNA mismatch repair

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Abstract

The genome of all organisms is constantly being challenged by endogenous and exogenous sources of DNA damage. Errors like base:base mismatches or small insertions and deletions, primarily introduced by DNA polymerases during DNA replication are repaired by an evolutionary conserved DNA mismatch repair (MMR) system. The MMR system, together with the DNA replication machinery, promote repair by an excision and resynthesis mechanism during or after DNA replication, increasing replication fidelity by up-to-three orders of magnitude. Consequently, inactivation of MMR genes results in elevated mutation rates that can lead to increased cancer susceptibility in humans. In this review, we summarize our current understanding of MMR with a focus on the different MMR protein complexes, their function and structure. We also discuss how recent findings have provided new insights in the spatio-temporal regulation and mechanism of MMR.

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Acknowledgments

The authors thank Dr. Christopher Putnam for critical reading of this review.

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Funding

This work was supported by the Harald zur Hausen Fellowship from the Deutsches Krebsforschungszentrum (DKFZ) and the Marie Curie Career Integration Grant “iMMR” (both granted to H.H.). R.K. was supported by the NIH grant GM50006 and the Ludwig Institute for Cancer Research.

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The authors declare that they have no conflict of interest.

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

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Authors and Affiliations

  1. German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Gloria X. Reyes, Tobias T. Schmidt & Hans Hombauer

  2. Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, Moores-UCSD Cancer Center and Institute of Genomic Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093-0669, USA

    Richard D. Kolodner

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  1. Gloria X. Reyes
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Reyes, G.X., Schmidt, T.T., Kolodner, R.D. et al. New insights into the mechanism of DNA mismatch repair. Chromosoma 124, 443–462 (2015). https://doi.org/10.1007/s00412-015-0514-0

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