Phosphorylation of Ago2 is required for its role in DNA double-strand break repair |
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| Authors: | Xiaolu Hu Yan Li Tianfang Zhang Lin Li She Chen Xiaohong Wu Haijun Li Binjie Qi Zuobing Chen |
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| Affiliation: | 1. Department of Rehabilitation Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China;2. Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;3. Tsinghua-Peking Center for Life Sciences, Beijing 100084, China;4. National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing 102206, China;1. State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China;2. Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China;3. Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China;4. Shenzhen Key Laboratory of Translational Medicine of Tumor, Department of Cell Biology and Genetics, Shenzhen University Health Sciences Center, Shenzhen, Guangdong 518060, China;5. University of Chinese Academy of Sciences, Beijing 100049, China;6. School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China;1. Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium;2. Department of Biomolecular Medicine, Ghent University, Ghent, Belgium;1. Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;2. The Institute of Translational Medicine, Zhejiang University, Hangzhou 310058, China;3. Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;4. Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan;5. Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310058, China;6. MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China;1. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;2. University of Chinese Academy of Sciences, Beijing 100089, China |
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| Abstract: | Repair of DNA double-strand break(DSB) is critical for the maintenance of genome integrity. A class of DSB-induced small RNAs(di RNAs) has been shown to play an important role in DSB repair. In humans,di RNAs are associated with Ago2 and guide the recruitment of Rad51 to DSB sites to facilitate repair by homologous recombination(HR). Ago2 activity has been reported to be regulated by phosphorylation under normal and hypoxic conditions. However, the role of Ago2 phosphorylation in DNA damage repair is unexplored. Here, we show that S672, S828, T830, and S831 of human Ago2 are phosphorylated in response to ionizing radiation(IR). S672 A mutation of Ago2 leads to significant reduction in Rad51 foci formation and HR efficiency. We further show that defective association of Ago2 S672 A variant with DSB sites, instead of defects in di RNA and Rad51 binding, may account for decreased Rad51 foci formation and HR efficiency.Our study reveals a novel regulatory mechanism for the function of Ago2 in DNA repair. |
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| Keywords: | Ago2 diRNA DNA repair Phosphorylation Small RNA |
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