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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Min Gao
  • Wei Wei
  • Ming Hua Li
  • Yong-Sheng Wu
  • Zhaoqing Ba
  • Kang-Xuan Jin
  • Miao-Miao Li
  • You-Qi Liao
  • Samir Adhikari
  • Zechen Chong
  • Ting Zhang
  • Cai-Xia Guo
  • Tie-Shan Tang
  • Bing-Tao Zhu
  • Xing-Zhi Xu
  • Mailand, Niels
  • Yun-Gui Yang
  • Yijun Qi
  • Jannie Michaela Rendtlew Danielsen
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.
Original languageEnglish
JournalCell Research
Issue number5
Pages (from-to)532-41
Number of pages10
Publication statusPublished - May 2014

ID: 110603359