An RNA Polymerase II-coupled function for histone H3K36 methylation in checkpoint activation and DSB repair

Histone modifications are major determinants of DNA double-strand break (DSB) response and repair. Here we elucidate a DSB repair function for transcription-coupled Set2 methylation at H3 lysine 36 (H3K36me). Cells devoid of Set2/H3K36me are hypersensitive to DNA-damaging agents and site-specific DSBs, fail to properly activate the DNA-damage checkpoint, and show genetic interactions with DSB-sensing and repair machinery. Set2/H3K36me3 is enriched at DSBs, and loss of Set2 results in altered chromatin architecture and inappropriate resection during G1 near break sites. Surprisingly, Set2 and RNA polymerase II are programmed for destruction after DSBs in a temporal manner—resulting in H3K36me3 to H3K36me2 transition that may be linked to DSB repair. Finally, we show a requirement of Set2 in DSB repair in transcription units—thus underscoring the importance of transcription-dependent H3K36me in DSB repair. Chromatin modifications play a fundamental role in regulating the cellular response to DNA damage. Here, Jha and Strahl identify methylation of histone H3 on lysine 36 mediated by the histone-methyltransferase Set2 as a regulator of chromatin remodelling at double-strand breaks that affects DNA repair.

• Publication year

  2014

• Venue

  Nature Communications

• Publication date

  2014-05-28

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/ncomms4965PMID 24910128PMCID 4052371
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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