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

被引:222
作者
Park, Ji-Hye
Park, Eun-Jung
Lee, Han-Sae
Kim, So Jung
Hur, Shin-Kyoung
Imbalzano, Anthony N.
Kwon, Jongbum [1 ]
机构
[1] Ewha Womans Univ, Dept Life Sci, Div Mol Life Sci, Seoul 120750, South Korea
[2] Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea
[3] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA
关键词
ATP-dependent chromatin remodeling; DNA double-strand break repair; gamma-H2AX; radiosensitivity; SWI/ SNF complex;
D O I
10.1038/sj.emboj.7601291
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3986 / 3997
页数:12
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