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

被引：183

作者：

D'Alessandro, Giuseppina ^{[1
]}

Whelan, Donna Rose ^{[2
]}

Howard, Sean Michael ^{[3
]}

Vitelli, Valerio ^{[1
]}

Renaudin, Xavier ^{[4
]}

Adamowicz, Marek ^{[1
,7
]}

Iannelli, Fabio ^{[1
]}

Jones-Weinert, Corey Winston ^{[1
]}

Lee, MiYoung ^{[4
]}

Matti, Valentina ^{[1
]}

Lee, Wei Ting C. ^{[2
]}

Morten, Michael John ^{[2
]}

Venkitaraman, Ashok Raraakrishnan ^{[4
]}

Cejka, Petr ^{[3
,5
]}

Rothenberg, Eli ^{[2
]}

di Fagagna, Fabrizio d'Adda ^{[1
,6
]}

机构：

[1] FIRC Inst Mol Oncol, IFOM, Via Adamello 16, I-20139 Milan, Italy

[2] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA

[3] Univ Svizzera Italiana, Inst Res Biomed, Via Vela 6, CH-6500 Bellinzona, Switzerland

[4] Univ Cambridge, Med Res Council, Canc Unit, Hills Rd, Cambridge CB2 0XZ, England

[5] Swiss Fed Inst Technol, Inst Biochem, Dept Biol, Otto Stern Weg 3, CH-8093 Zurich, Switzerland

[6] CNR, IGM, Via Abbiategrasso 207, I-27100 Pavia, Italy

[7] Univ Sussex, Sch Life Sci, Genome Damage & Stabil Ctr, Brighton BN1 9RH, E Sussex, England

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

欧洲研究理事会; 瑞士国家科学基金会; 英国医学研究理事会;

关键词：

DOUBLE-STRAND BREAK; DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION; POLYMERASE-II; GOUTIERES-SYNDROME; END RESECTION; NASCENT RNA; REPAIR; REPLICATION; PROTEIN;

D O I：

10.1038/s41467-018-07799-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 HRmediated repair.

引用

页数：17

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