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RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair.

ABSTRACT: Unrestrained 53BP1 activity at DNA double-strand breaks (DSBs) hampers DNA end resection and upsets DSB repair pathway choice. RNF169 acts as a molecular rheostat to limit 53BP1 deposition at DSBs, but how this fine balance translates to DSB repair control remains undefined. In striking contrast to 53BP1, ChIP analyses of AsiSI-induced DSBs unveiled that RNF169 exhibits robust accumulation at DNA end-proximal regions and preferentially targets resected, RPA-bound DSBs. Accordingly, we found that RNF169 promotes CtIP-dependent DSB resection and favors homology-mediated DSB repair, and further showed that RNF169 dose-dependently stimulates single-strand annealing repair, in part, by alleviating the 53BP1-imposed barrier to DSB end resection. Our results highlight the interplay of RNF169 with 53BP1 in fine-tuning choice of DSB repair pathways.

SUBMITTER: An L

PROVIDER: S-EPMC6126738 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair.

An Liwei L Dong Chao C Li Junshi J Chen Jie J Yuan Jingsong J Huang Jun J Chan Kui Ming KM Yu Cheng-Han CH Huen Michael S Y MSY

Proceedings of the National Academy of Sciences of the United States of America 20180813 35

Unrestrained 53BP1 activity at DNA double-strand breaks (DSBs) hampers DNA end resection and upsets DSB repair pathway choice. RNF169 acts as a molecular rheostat to limit 53BP1 deposition at DSBs, but how this fine balance translates to DSB repair control remains undefined. In striking contrast to 53BP1, ChIP analyses of A<i>si</i>SI-induced DSBs unveiled that RNF169 exhibits robust accumulation at DNA end-proximal regions and preferentially targets resected, RPA-bound DSBs. Accordingly, we fou ...[more]

PMID: 30104380

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