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Critical role of lysine 134 methylation on histone H2AX for γ-H2AX production and DNA repair

Author

Listed:
  • Kenbun Sone

    (Section of Hematology/Oncology, University of Chicago)

  • Lianhua Piao

    (Section of Hematology/Oncology, University of Chicago)

  • Makoto Nakakido

    (Section of Hematology/Oncology, University of Chicago)

  • Koji Ueda

    (Graduate School of Frontier Sciences, The University of Tokyo)

  • Thomas Jenuwein

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Yusuke Nakamura

    (Section of Hematology/Oncology, University of Chicago)

  • Ryuji Hamamoto

    (Section of Hematology/Oncology, University of Chicago
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo)

Abstract

The presence of phosphorylated histone H2AX (γ-H2AX) is associated with the local activation of DNA-damage repair pathways. Although γ-H2AX deregulation in cancer has previously been reported, the molecular mechanism involved and its relationship with other histone modifications remain largely unknown. Here we find that the histone methyltransferase SUV39H2 methylates histone H2AX on lysine 134. When H2AX was mutated to abolish K134 methylation, the level of γ-H2AX became significantly reduced. We also found lower γ-H2AX activity following the introduction of double-strand breaks in Suv39h2 knockout cells or on SUV39H2 knockdown. Tissue microarray analyses of clinical lung and bladder tissues also revealed a positive correlation between H2AX K134 methylation and γ-H2AX levels. Furthermore, introduction of K134-substituted histone H2AX enhanced radio- and chemosensitivity of cancer cells. Overall, our results suggest that H2AX methylation plays a role in the regulation of γ-H2AX abundance in cancer.

Suggested Citation

  • Kenbun Sone & Lianhua Piao & Makoto Nakakido & Koji Ueda & Thomas Jenuwein & Yusuke Nakamura & Ryuji Hamamoto, 2014. "Critical role of lysine 134 methylation on histone H2AX for γ-H2AX production and DNA repair," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6691
    DOI: 10.1038/ncomms6691
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