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The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage

Author

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  • Haiqing Fu

    (Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Melvenia M. Martin

    (Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Marie Regairaz

    (Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Liang Huang

    (Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Yang You

    (Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Chi-Mei Lin

    (Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Michael Ryan

    (InSilico Solutions)

  • RyangGuk Kim

    (InSilico Solutions)

  • Tsutomu Shimura

    (National Institute of Public Health 2-3-6 Minami)

  • Yves Pommier

    (Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Mirit I. Aladjem

    (Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

Abstract

The Mus81 endonuclease resolves recombination intermediates and mediates cellular responses to exogenous replicative stress. Here, we show that Mus81 also regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events. In the absence of Mus81 endonuclease activity, DNA synthesis is slowed and replication initiation events are more frequent. In addition, Mus81-deficient cells fail to recover from exposure to low doses of replication inhibitors and cell viability is dependent on the XPF endonuclease. Despite an increase in replication initiation frequency, cells lacking Mus81 use the same pool of replication origins as Mus81-expressing cells. Therefore, decelerated DNA replication in Mus81-deficient cells does not initiate from cryptic or latent origins not used during normal growth. These results indicate that Mus81 plays a key role in determining the rate of DNA replication without activating a novel group of replication origins.

Suggested Citation

  • Haiqing Fu & Melvenia M. Martin & Marie Regairaz & Liang Huang & Yang You & Chi-Mei Lin & Michael Ryan & RyangGuk Kim & Tsutomu Shimura & Yves Pommier & Mirit I. Aladjem, 2015. "The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7746
    DOI: 10.1038/ncomms7746
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