RRC ID 54781
著者 D'Alessandro G, Whelan DR, Howard SM, Vitelli V, Renaudin X, Adamowicz M, Iannelli F, Jones-Weinert CW, Lee M, Matti V, Lee WTC, Morten MJ, Venkitaraman AR, Cejka P, Rothenberg E, d'Adda di Fagagna F.
タイトル BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment.
ジャーナル Nat Commun
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.
巻・号 9(1)
ページ 5376
公開日 2018-12-18
DOI 10.1038/s41467-018-07799-2
PII 10.1038/s41467-018-07799-2
PMID 30560944
PMC PMC6299093
MeSH BRCA1 Protein / genetics BRCA1 Protein / metabolism* BRCA2 Protein / genetics BRCA2 Protein / metabolism* Cell Line, Tumor DNA / genetics DNA / metabolism DNA Breaks, Double-Stranded G2 Phase / genetics Gene Knockdown Techniques HEK293 Cells Humans RNA, Long Noncoding / genetics RNA, Long Noncoding / metabolism* RNA, Small Interfering / metabolism Rad51 Recombinase / genetics Rad51 Recombinase / metabolism Recombinational DNA Repair* Ribonuclease H / genetics Ribonuclease H / metabolism* S Phase / genetics
IF 11.878
引用数 35
リソース情報
ヒト・動物細胞 HeLa/Fucci(RCB2812)