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

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.
Mesh Terms:
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
Nat Commun
Date: Dec. 18, 2017
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