USP51 deubiquitylates H2AK13,15ub and regulates DNA damage response

Zhiquan Wang, Honglian Zhang, Ji Liu, Abigael Cheruiyot, Jeong Heon Lee, Tamas Ordog, Zhenkun Lou, Zhongsheng You, Zhiguo Zhang

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Dynamic regulation of RNF168-mediated ubiquitylation of histone H2A Lys13,15 (H2AK13,15ub) at DNA doublestrand breaks (DSBs) is crucial for preventing aberrant DNA repair and maintaining genome stability. However, it remains unclear which deubiquitylating enzyme (DUB) removes H2AK13,15ub. Here we show that USP51, a previously uncharacterized DUB, deubiquitylates H2AK13,15ub and regulates DNA damage response. USP51 depletion results in increased spontaneous DNA damage foci and elevated levels of H2AK15ub and impairs DNA damage response. USP51 overexpression suppresses the formation of ionizing radiation-induced 53BP1 and BRCA1 but not RNF168 foci, suggesting that USP51 functions downstream from RNF168 in DNA damage response. In vitro, USP51 binds to H2A–H2B directly and deubiquitylates H2AK13,15ub. In cells, USP51 is recruited to chromatin after DNA damage and regulates the dynamic assembly/disassembly of 53BP1 and BRCA1 foci. These results show that USP51 is the DUB for H2AK13,15ub and regulates DNA damage response.

Original languageEnglish (US)
Pages (from-to)946-959
Number of pages14
JournalGenes and Development
Issue number8
StatePublished - Apr 15 2016


  • DNA damage response
  • Deubiqutylating enzyme
  • H2AK15ub
  • USP51

ASJC Scopus subject areas

  • General Medicine


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