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  • The EMBO Journal (2006) 25, 3986 - 3997
  • doi:10.1038/sj.emboj.7601291

Published online: 24 August 2006

Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting big gamma-H2AX induction

Ji-Hye Park1, Eun-Jung Park1, Han-Sae Lee1, So Jung Kim1, Shin-Kyoung Hur1, Anthony N Imbalzano2 and Jongbum Kwon1

  1. Division of Molecular Life Sciences, Department of Life Science and Center for Cell Signaling Research, Ewha Woman's University, Seoul, Korea
  2. Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, Massachusetts, USA

Correspondence to:

Jongbum Kwon, Division of Molecular Life Sciences, Department of Life Science and Center for Cell Signaling Research, Ewha Woman's University, Seoul 120-750, Korea. Tel.: +82 2 3277 4334; Fax: +82 2 3277 3760; E-mail: jongkwon@ewha.ac.kr

Received 15 September 2005; Accepted 27 July 2006

Although mammalian SWI/SNF chromatin remodeling complexes have been well established to play important role in transcription, their role in DNA repair has remained largely unexplored. Here we show that inactivation of the SWI/SNF complexes and downregulation of the catalytic core subunits of the complexes both result in inefficient DNA double-strand break (DSB) repair and increased DNA damage sensitivity as well as a large defect in H2AX phosphorylation (gamma-H2AX) and nuclear focus formation after DNA damage. The expression of most DSB repair genes remains unaffected and DNA damage checkpoints are grossly intact in the cells inactivated for the SWI/SNF complexes. Although the SWI/SNF complexes do not affect the expression of ATM, DNA-PK and ATR, or their activation and/or recruitment to DSBs, they rapidly bind to DSB-surrounding chromatin via interaction with gamma-H2AX in the manner that is dependent on the amount of DNA damage. Given the crucial role for gamma-H2AX in efficient DSB repair, these results suggest that the SWI/SNF complexes facilitate DSB repair, at least in part, by promoting H2AX phosphorylation by directly acting on chromatin.

  • Keywords:

    • ATP-dependent chromatin remodeling,
    • DNA double-strand break repair,
    • gamma-H2AX,
    • radiosensitivity,
    • SWI/SNF complex