title: Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination.
abstract: 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 important 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 Rad51 and that the interaction is enhanced in cells treated with ionizing radiation. We demonstrate that Rad51 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 Mre11 loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating Rad51 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or retention at DSBs to facilitate repair by HR.
authors.affiliation: 1] Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: 1] Tsinghua-Peking Center for Life Sciences, Beijing 100084, China [2] Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: 1] Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Li
authors.affiliation: Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Wu
authors.affiliation: 1] Tsinghua-Peking Center for Life Sciences, Beijing 100084, China [2] Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Ba
authors.affiliation: 1] Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Kang-Xuan
authors.initials: KX
authors.lastname: Jin
authors.affiliation: 1] Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Li
authors.affiliation: 1] Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: You-Qi
authors.initials: YQ
authors.lastname: Liao
authors.affiliation: 1] Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Samir
authors.initials: S
authors.lastname: Adhikari
authors.affiliation: Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zechen
authors.initials: Z
authors.lastname: Chong
authors.affiliation: Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Tie-Shan
authors.initials: TS
authors.lastname: Tang
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Sciences, Capital Normal University, Beijing 100048, China.
authors.forename: Bing-Tao
authors.initials: BT
authors.lastname: Zhu
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Sciences, Capital Normal University, Beijing 100048, China.
authors.forename: Xing-Zhi
authors.initials: XZ
authors.lastname: Xu
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Ubiquitin Signalling Group, Faculty of Health Sciences, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Mailand
authors.affiliation: 1] Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yun-Gui
authors.initials: YG
authors.lastname: Yang
authors.affiliation: 1] Tsinghua-Peking Center for Life Sciences, Beijing 100084, China [2] Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Qi
authors.affiliation: 1] Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] The Novo Nordisk Foundation Center for Protein Research, Ubiquitin Signalling Group, Faculty of Health Sciences, Copenhagen, Denmark.
authors.forename: Jannie M
authors.initials: JM
authors.lastname: Rendtlew Danielsen
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism*; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D059765:Homologous Recombination; D006801:Humans; D060066:Protein Interaction Maps; D012313:RNA / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D012313:RNA; D051135:Rad51 Recombinase; D043244:Ribonuclease III