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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Liwei An
  • Chao Dong
  • Junshi Li
  • Jie Chen
  • Jingsong Yuan
  • Jun Huang
  • Cheng-Han Yu
  • Michael S. Y. Huen

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)E8286-E8295
Journal / PublicationProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number35
Online published13 Aug 2018
Publication statusPublished - 28 Aug 2018

Link(s)

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.

Research Area(s)

  • 53BP1, DNA damage, DNA double-strand breaks, RNF169, Single-strand annealing repair

Citation Format(s)

RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair. / An, Liwei; Dong, Chao; Li, Junshi; Chen, Jie; Yuan, Jingsong; Huang, Jun; Chan, Kui Ming; Yu, Cheng-Han; Huen, Michael S. Y.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 35, 28.08.2018, p. E8286-E8295.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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