Nature 458, 591-596 (2 April 2009) | doi:10.1038/nature07849; Received 10 December 2008; Accepted 4 February 2009; Published online 22 February 2009

Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions

Peter J. Cook1,2,5, Bong Gun Ju1,3,5, Francesca Telese1, Xiangting Wang1, Christopher K. Glass4 & Michael G. Rosenfeld1

  1. Howard Hughes Medical Institute School of Medicine, University of California, San Diego, California 92037, USA
  2. Department of Biology Graduate Program, School of Medicine, University of California, San Diego, California 92093, USA
  3. Department of Life Science, Sogang University, Seoul 121-742, Korea
  4. Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
  5. These authors contributed equally to this work.

Correspondence to: Michael G. Rosenfeld1 Correspondence and requests for materials should be addressed to M.G.R. (Email:


Life and death fate decisions allow cells to avoid massive apoptotic death in response to genotoxic stress. Although the regulatory mechanisms and signalling pathways controlling DNA repair and apoptosis are well characterized, the precise molecular strategies that determine the ultimate choice of DNA repair and survival or apoptotic cell death remain incompletely understood. Here we report that a protein tyrosine phosphatase, EYA, is involved in promoting efficient DNA repair rather than apoptosis in response to genotoxic stress in mammalian embryonic kidney cells by executing a damage-signal-dependent dephosphorylation of an H2AX carboxy-terminal tyrosine phosphate (Y142). This post-translational modification determines the relative recruitment of either DNA repair or pro-apoptotic factors to the tail of serine phosphorylated histone H2AX (gamma-H2AX) and allows it to function as an active determinant of repair/survival versus apoptotic responses to DNA damage, revealing an additional phosphorylation-dependent mechanism that modulates survival/apoptotic decisions during mammalian organogenesis.


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