Journal
EMBO JOURNAL
Volume 29, Issue 8, Pages 1434-1445Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.27
Keywords
DNA double-strand break repair; Gcn5; H2AX phosphorylation; histone acetylation; SWI/SNF chromatin remodelling complex
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Funding
- Korea Ministry of Education, Science and Technology (MEST) [R01-2007-000-10571-0]
- National Research Foundation of Korea [2007-0053458, 2007-03886, R01-2007-000-10571-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Although recent studies highlight the importance of histone modifications and ATP-dependent chromatin remodelling in DNA double-strand break (DSB) repair, how these mechanisms cooperate has remained largely unexplored. Here, we show that the SWI/SNF chromatin remodelling complex, earlier known to facilitate the phosphorylation of histone H2AX at Ser-139 (S139ph) after DNA damage, binds to gamma-H2AX (the phosphorylated form of H2AX)-containing nucleosomes in S139ph-dependent manner. Unexpectedly, BRG1, the catalytic subunit of SWI/SNF, binds to gamma-H2AX nucleosomes by interacting with acetylated H3, not with S139ph itself, through its bromodomain. Blocking the BRG1 interaction with gamma-H2AX nucleosomes either by deletion or overexpression of the BRG1 bromodomain leads to defect of S139ph and DSB repair. H3 acetylation is required for the binding of BRG1 to gamma-H2AX nucleosomes. S139ph stimulates the H3 acetylation on gamma-H2AX nucleosomes, and the histone acetyltransferase Gcn5 is responsible for this novel crosstalk. The H3 acetylation on gamma-H2AX nucleosomes is induced by DNA damage. These results collectively suggest that SWI/ SNF, gamma-H2AX and H3 acetylation cooperatively act in a feedback activation loop to facilitate DSB repair. The EMBO Journal (2010) 29, 1434-1445. doi: 10.1038/emboj.2010.27; Published online 11 March 2010
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