BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment
| Autor: | D'Alessandro, Giuseppina, Whelan, Donna Rose, Howard, Sean Michael, Vitelli, Valerio, Renaudin, Xavier, Adamowicz, Marek, Iannelli, Fabio, Jones-Weinert, Corey Winston, Lee, MiYoung, Matti, Valentina, Lee, Wei Ting C., Morten, Michael John, Venkitaraman, Ashok Raraakrishnan, Cejka, Petr, Rothenberg, Eli, di Fagagna, Fabrizio d'Adda |
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| Jazyk: | angličtina |
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| ISSN: | 2041-1723 |
| Popis: | 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. Nature Communications, 9 ISSN:2041-1723 |
| Databáze: | OpenAIRE |
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