A cooperative activation loop among SWI/SNF, γ-H2AX and H3 acetylation for DNA double-strand break repair

Han Sae Lee, Ji Hye Park, So Jung Kim, Su Jung Kwon, Jongbum Kwon

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

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 γ-H2AX (the phosphorylated form of H2AX)-containing nucleosomes in S139ph-dependent manner. Unexpectedly, BRG1, the catalytic subunit of SWI/SNF, binds to γ-H2AX nucleosomes by interacting with acetylated H3, not with S139ph itself, through its bromodomain. Blocking the BRG1 interaction with γ-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 γ-H2AX nucleosomes. S139ph stimulates the H3 acetylation on γ-H2AX nucleosomes, and the histone acetyltransferase Gcn5 is responsible for this novel crosstalk. The H3 acetylation on γ-H2AX nucleosomes is induced by DNA damage. These results collectively suggest that SWI/SNF, γ-H2AX and H3 acetylation cooperatively act in a feedback activation loop to facilitate DSB repair.

Original languageEnglish
Pages (from-to)1434-1445
Number of pages12
JournalEMBO Journal
Volume29
Issue number8
DOIs
StatePublished - Apr 2010

Keywords

  • DNA double-strand break repair
  • Gcn5
  • H2AX phosphorylation
  • Histone acetylation
  • SWI/SNF chromatin remodelling complex

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