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BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment.

Published version
Peer-reviewed

Type

Article

Change log

Authors

D'Alessandro, Giuseppina 
Whelan, Donna Rose 
Howard, Sean Michael 
Vitelli, Valerio 
Renaudin, Xavier 

Abstract

DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA:RNA hybrid levels at DSBs. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair.

Description

Keywords

BRCA1 Protein, BRCA2 Protein, Cell Line, Tumor, DNA, DNA Breaks, Double-Stranded, G2 Phase, Gene Knockdown Techniques, HEK293 Cells, Humans, RNA, Long Noncoding, RNA, Small Interfering, Rad51 Recombinase, Recombinational DNA Repair, Ribonuclease H, S Phase

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

9

Publisher

Nature Publishing Group
Sponsorship
Medical Research Council (MC_UU_12022/1)
Medical Research Council (MC_PC_17111)
MRC (MC_UU_12022/8)
Medical Research Council (MC_PC_15050)