Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

• Published in: Cell research Vol. 24; no. 5; pp. 532 - 541
• Main Authors: Gao, Min, Wei, Wei, Li, Ming-Ming, Wu, Yong-Sheng, Ba, Zhaoqing, Jin, Kang-Xuan, Li, Miao-Miao, Liao, You-Qi, Adhikari, Samir, Chong, Zechen, Zhang, Ting, Guo, Cai-Xia, Tang, Tie-shan, Zhu, Bing-Tao, Xu, Xing-Zhi, Mailand, Niels, Yang, Yun-Gui, Qi, Yijun, Danielsen, Jannie M Rendtlew
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2014; Nature Publishing Group
• Subjects: 631/337/1427/2122; 631/337/1427/2190; Accumulation; Argonaute Proteins - metabolism; Biomedical and Life Sciences; Cell Biology; Cell Line; Deoxyribonucleic acid; Dicer酶; DNA; DNA Breaks, Double-Stranded; DNA Repair; DNA双链断裂; e蛋白; Homologous Recombination; Humans; Ionizing radiation; Lesions; Life Sciences; Mammals; Original; original-article; Protein Interaction Maps; Rad51 Recombinase - metabolism; Retention; Ribonuclease III - metabolism; RNA - metabolism; 同源重组; 哺乳动物细胞; 招聘; 断裂修复; 细胞毒性; Rad51; diRNA; DSB; Ago2; Homologous recombination
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2014.36

DNA double-strand breaks （DSBs） are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs （diRNAs） is produced from sequences around DSB sites. DiRNAs are associated with Argonaute （Ago） proteins and play an im- portant role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination （HR） and that it specifically relies on the effector protein Ago2 in mammalian cells. Interestingly, we show that Ago2 forms a complex with RadS1 and that the interaction is enhanced in cells treated with ionizing radiation. We demonstrate that RadS1 accumulation at DSB sites and HR repair depend on catalytic activity and small RNA-binding capability of Ago2. In contrast, DSB resection as well as RPA and Mrell loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating RadS1 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote RadS1 recruitment and/or retention at DSBs to facilitate repair by HR.