RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair
- Proc Natl Acad Sci U S A. 2018 Aug 28;115(35):E8286-E8295. doi: 10.1073/pnas.1804823115.
- 1. School of Biomedical Sciences, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong S.A.R.
- 2. Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P.R. China.
- 3. Department of Radiation Oncology, Center for Radiological Research, Columbia University Medical Center, NY 10032.
- 4. Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
- 5. Department of Biomedical Sciences, City University of Hong Kong, Hong Kong S.A.R.
- 6. School of Biomedical Sciences, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong S.A.R.; [email protected].
- 7. State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong S.A.R.
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.