期刊
EMBO JOURNAL
卷 31, 期 11, 页码 2511-2527出版社
WILEY
DOI: 10.1038/emboj.2012.104
关键词
chromatin; DNA damage response; DSB repair; histone ubiquitin ligase; RNF8
资金
- Swedish Cancer Society
- European Community Network of Excellence RUBICON [LSHC-CT-2005-018683]
- Swedish Research Council
- Netherlands Organization for Scientific Research (NWO)
- European Molecular Biology Organization (EMBO)
- Federation of European Biochemical Societies (FEBS)
- Human Frontier Science Program (HFSP-CDA)
The ubiquitin ligases RNF8 and RNF168 orchestrate DNA damage signalling through the ubiquitylation of histone H2A and the recruitment of downstream repair factors. Here, we demonstrate that RNF8, but not RNF168 or the canonical H2A ubiquitin ligase RNF2, mediates extensive chromatin decondensation. Our data show that CHD4, the catalytic subunit of the NuRD complex, interacts with RNF8 and is essential for RNF8-mediated chromatin unfolding. The chromatin remodelling activity of CHD4 promotes efficient ubiquitin conjugation and assembly of RNF168 and BRCA1 at DNA double-strand breaks. Interestingly, RNF8-mediated recruitment of CHD4 and subsequent chromatin remodelling were independent of the ubiquitin-ligase activity of RNF8, but involved a non-canonical interaction with the forkhead-associated (FHA) domain. Our study reveals a new mechanism of chromatin remodelling-assisted ubiquitylation, which involves the cooperation between CHD4 and RNF8 to create a local chromatin environment that is permissive to the assembly of checkpoint and repair machineries at DNA lesions. The EMBO Journal (2012) 31, 2511-2527. doi: 10.1038/emboj.2012.104; Published online 24 April 2012
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