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WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity

Author

Listed:
  • Andrew Xiao

    (Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10065, USA)

  • Haitao Li

    (Structural Biology Program,)

  • David Shechter

    (Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10065, USA)

  • Sung Hee Ahn

    (Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10065, USA)

  • Laura A. Fabrizio

    (Molecular Biology Program, Memorial-Sloan-Kettering Cancer Center, New York, New York 10065, USA)

  • Hediye Erdjument-Bromage

    (Molecular Biology Program, Memorial-Sloan-Kettering Cancer Center, New York, New York 10065, USA)

  • Satoko Ishibe-Murakami

    (Structural Biology Program,)

  • Bin Wang

    (Howard Hughes Medical Institute, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Paul Tempst

    (Molecular Biology Program, Memorial-Sloan-Kettering Cancer Center, New York, New York 10065, USA)

  • Kay Hofmann

    (Miltenyi Biotec GmbH)

  • Dinshaw J. Patel

    (Structural Biology Program,)

  • Stephen J. Elledge

    (Howard Hughes Medical Institute, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • C. David Allis

    (Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10065, USA)

Abstract

DNA double-stranded breaks present a serious challenge for eukaryotic cells. The inability to repair breaks leads to genomic instability, carcinogenesis and cell death. During the double-strand break response, mammalian chromatin undergoes reorganization demarcated by H2A.X Ser 139 phosphorylation (γ-H2A.X). However, the regulation of γ-H2A.X phosphorylation and its precise role in chromatin remodelling during the repair process remain unclear. Here we report a new regulatory mechanism mediated by WSTF (Williams–Beuren syndrome transcription factor, also known as BAZ1B)—a component of the WICH complex (WSTF–ISWI ATP-dependent chromatin-remodelling complex). We show that WSTF has intrinsic tyrosine kinase activity by means of a domain that shares no sequence homology to any known kinase fold. We show that WSTF phosphorylates Tyr 142 of H2A.X, and that WSTF activity has an important role in regulating several events that are critical for the DNA damage response. Our work demonstrates a new mechanism that regulates the DNA damage response and expands our knowledge of domains that contain intrinsic tyrosine kinase activity.

Suggested Citation

  • Andrew Xiao & Haitao Li & David Shechter & Sung Hee Ahn & Laura A. Fabrizio & Hediye Erdjument-Bromage & Satoko Ishibe-Murakami & Bin Wang & Paul Tempst & Kay Hofmann & Dinshaw J. Patel & Stephen J. E, 2009. "WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity," Nature, Nature, vol. 457(7225), pages 57-62, January.
    • Handle: RePEc:nat:nature:v:457:y:2009:i:7225:d:10.1038_nature07668
    DOI: 10.1038/nature07668
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    Cited by:

    1. Jessica L. Kelliher & Melissa L. Folkerts & Kaiyuan V. Shen & Wan Song & Kyle Tengler & Clara M. Stiefel & Seong-Ok Lee & Eloise Dray & Weixing Zhao & Brian Koss & Nicholas R. Pannunzio & Justin W. Le, 2024. "Evolved histone tail regulates 53BP1 recruitment at damaged chromatin," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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