Journal Article

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

Matti, Valentina, Lee, Wei Ting C., Adamowicz, Marek, Whelan, Donna Rose, Cejka, Petr, Rothenberg, Eli, Renaudin, Xavier, D’Alessandro, Giuseppina, d’Adda di Fagagna, Fabrizio, Venkitaraman, Ashok Raraakrishnan, Morten, Michael John, Howard, Sean Michael, Lee, MiYoung, Jones-Weinert, Corey Winston, Vitelli, Valerio, Iannelli, Fabio

2018

Overview

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. Long non-coding RNAs transcribed at DNA damaged sites can play part in DNA damage response. Here the authors reveal that damaged induced lncRNAs can form DNA:RNA hybrids at resected DNA-ends. These hybrids are involved in recruiting HR-mediated repair machinery which, in turn, controls their level at DSBs.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/19 / 45/77 / 45/88 / 49/109 / 49/15 / 49/22 / 49/31 / 49/90 / 631/67 / 631/80 / 96/63 / BRCA1 protein / BRCA1 Protein - genetics / BRCA1 Protein - metabolism / BRCA2 protein / BRCA2 Protein - genetics / BRCA2 Protein - metabolism / Breast cancer / Cell death / Cell Line, Tumor / Deoxyribonucleic acid / DNA / DNA - genetics / DNA - metabolism / DNA Breaks, Double-Stranded / DNA damage / G2 Phase - genetics / Gene Knockdown Techniques / Genomic instability / HEK293 Cells / Homologous recombination / Homology / Humanities and Social Sciences / Humans / Hybrids / Lesions / Localization / multidisciplinary / Proteins / Rad51 Recombinase - genetics / Rad51 Recombinase - metabolism / Recombinational DNA Repair / Recruitment / Repair / Ribonuclease H - genetics / Ribonuclease H - metabolism / Ribonuclease H2 / Ribonucleic acid / RNA / RNA, Long Noncoding - genetics / RNA, Long Noncoding - metabolism / RNA, Small Interfering - metabolism / S Phase - genetics / Science / Science (multidisciplinary) / Senescence / Stability / Yeast