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

Andrew Xiao1, Haitao Li, David Shechter

  • 1Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10065, USA.

Nature
|December 19, 2008
PubMed

Insights

Williams-Beuren syndrome transcription factor (WSTF) has novel tyrosine kinase activity, phosphorylating H2A.X to regulate DNA damage response and chromatin remodelling in eukaryotic cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • DNA double-stranded breaks (DSBs) pose significant threats to genomic stability in eukaryotic cells.
  • The cellular response involves chromatin reorganization marked by H2A.X phosphorylation (gamma-H2A.X).
  • Mechanisms regulating gamma-H2A.X and its role in chromatin remodeling during DNA repair are not fully understood.

Purpose of the Study:

  • To elucidate the regulatory mechanism of gamma-H2A.X phosphorylation during the DNA damage response.
  • To investigate the role of Williams-Beuren syndrome transcription factor (WSTF) in DNA repair.
  • To identify novel kinase activities involved in chromatin remodeling.

Main Methods:

  • Investigated the enzymatic activity of WSTF, a component of the WICH complex.
  • Utilized biochemical assays to detect tyrosine kinase activity within WSTF.
  • Analyzed the phosphorylation of H2A.X at Tyr 142 by WSTF in the context of DNA damage.

Main Results:

  • Discovered that WSTF possesses intrinsic tyrosine kinase activity through a unique domain.
  • Demonstrated that WSTF directly phosphorylates H2A.X at Tyr 142.
  • Showed WSTF activity is crucial for regulating key events in the DNA damage response pathway.

Conclusions:

  • Identified a novel regulatory mechanism for the DNA damage response mediated by WSTF.
  • Expanded the understanding of protein domains with intrinsic tyrosine kinase activity.
  • Highlighted WSTF's critical role in maintaining genomic integrity through H2A.X phosphorylation and chromatin remodeling.

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