Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination
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Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination. / Gao, Min; Wei, Wei; Li, Ming Hua; 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 Michaela Rendtlew.
In: Cell Research, Vol. 24, No. 5, 05.2014, p. 532-41.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination
AU - Gao, Min
AU - Wei, Wei
AU - Li, Ming Hua
AU - Wu, Yong-Sheng
AU - Ba, Zhaoqing
AU - Jin, Kang-Xuan
AU - Li, Miao-Miao
AU - Liao, You-Qi
AU - Adhikari, Samir
AU - Chong, Zechen
AU - Zhang, Ting
AU - Guo, Cai-Xia
AU - Tang, Tie-Shan
AU - Zhu, Bing-Tao
AU - Xu, Xing-Zhi
AU - Mailand, Niels
AU - Yang, Yun-Gui
AU - Qi, Yijun
AU - Danielsen, Jannie Michaela Rendtlew
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
U2 - 10.1038/cr.2014.36
DO - 10.1038/cr.2014.36
M3 - Journal article
C2 - 24662483
VL - 24
SP - 532
EP - 541
JO - Cell Research
JF - Cell Research
SN - 1001-0602
IS - 5
ER -
ID: 110603359