TY - JOUR
T1 - USP51 deubiquitylates H2AK13,15ub and regulates DNA damage response
AU - Wang, Zhiquan
AU - Zhang, Honglian
AU - Liu, Ji
AU - Cheruiyot, Abigael
AU - Lee, Jeong Heon
AU - Ordog, Tamas
AU - Lou, Zhenkun
AU - You, Zhongsheng
AU - Zhang, Zhiguo
N1 - Publisher Copyright:
© 2016 Wang et al.
PY - 2016/4/15
Y1 - 2016/4/15
N2 - 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.
AB - 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.
KW - DNA damage response
KW - Deubiqutylating enzyme
KW - H2AK15ub
KW - USP51
UR - http://www.scopus.com/inward/record.url?scp=84963837773&partnerID=8YFLogxK
U2 - 10.1101/gad.271841.115
DO - 10.1101/gad.271841.115
M3 - Article
C2 - 27083998
AN - SCOPUS:84963837773
SN - 0890-9369
VL - 30
SP - 946
EP - 959
JO - Genes and Development
JF - Genes and Development
IS - 8
ER -