Reference - Detail
| RRC ID | 54781 |
|---|---|
| Author | 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. |
| Title | BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment. |
| Journal | 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. |
| Volume | 9(1) |
| Pages | 5376 |
| Published | 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 |
| Times Cited | 35 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 59 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HeLa/Fucci(RCB2812) |