A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response (original) (raw)

Nature volume 436, pages 294–298 (2005)Cite this article

Abstract

DNA breaks are extremely harmful lesions that need to be repaired efficiently throughout the genome. However, the packaging of DNA into nucleosomes is a significant barrier to DNA repair, and the mechanisms of repair in the context of chromatin are poorly understood1. Here we show that lysine 56 (K56) acetylation is an abundant modification of newly synthesized histone H3 molecules that are incorporated into chromosomes during S phase. Defects in the acetylation of K56 in histone H3 result in sensitivity to genotoxic agents that cause DNA strand breaks during replication. In the absence of DNA damage, the acetylation of histone H3 K56 largely disappears in G2. In contrast, cells with DNA breaks maintain high levels of acetylation, and the persistence of the modification is dependent on DNA damage checkpoint proteins. We suggest that the acetylation of histone H3 K56 creates a favourable chromatin environment for DNA repair and that a key component of the DNA damage response is to preserve this acetylation.

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Acknowledgements

We thank W. Bonner, M. Christman, J. Diffley, L. Drury, P. Fitzjohn, H. Nash, A. Kristjuhan, D. Lyon, C. Redon, D. Stillman, J. Svejstrup and S. Tanaka for reagents, and A. Castillo and A. Gunjan for critical reading of the manuscript. This work was funded by Cancer Research UK and the International Association for Cancer Research. H.M. was supported by postdoctoral fellowships from the NAITO Foundation and Cancer Research UK.

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Authors and Affiliations

  1. Chromosome Dynamics Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire, EN6 3LD, UK
    Hiroshi Masumoto & Alain Verreault
  2. Department of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Texas, 77030, Houston, USA
    David Hawke & Ryuji Kobayashi

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  1. Hiroshi Masumoto
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  2. David Hawke
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  3. Ryuji Kobayashi
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  4. Alain Verreault
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Correspondence toAlain Verreault.

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Masumoto, H., Hawke, D., Kobayashi, R. et al. A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response.Nature 436, 294–298 (2005). https://doi.org/10.1038/nature03714

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