Journal Article

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

Yuan, Jingsong, Chan, Kui Ming, An, Liwei, Dong, Chao, Li, Junshi, Yu, Cheng-han, Huen, Michael S. Y., Chen, Jie, Huang, Jun

2018

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Annealing / Biological Sciences / Carrier Proteins - genetics / Carrier Proteins - metabolism / Cell Line, Tumor / Cloning / Deoxyribonucleic acid / Deposition / DNA / DNA - genetics / DNA - metabolism / DNA Breaks, Double-Stranded / DNA damage / DNA Repair - physiology / Double-strand break repair / Genetic engineering / Genetics / Homology / Humans / Nuclear Proteins - genetics / Nuclear Proteins - metabolism / PNAS Plus / Repair / Tumor Suppressor p53-Binding Protein 1 - genetics / Tumor Suppressor p53-Binding Protein 1 - metabolism / Ubiquitin-Protein Ligases - genetics / Ubiquitin-Protein Ligases - metabolism