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.

authors

An L,Dong C,Li J,Chen J,Yuan J,Huang J,Chan KM,Yu CH,Huen MSY

doi

10.1073/pnas.1804823115

subject

Has Abstract

pub_date

2018-08-28 00:00:00

pages

E8286-E8295

issue

35

eissn

0027-8424

issn

1091-6490

pii

1804823115

journal_volume

115

pub_type

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