Yan Li
Tianfang Zhang
Lin Li
She Chen
Xiaohong Wu
Haijun Li
Binjie Qi
Zuobing Chen
a Department of Rehabilitation Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China;
b Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;
c Tsinghua-Peking Center for Life Sciences, Beijing 100084, China;
d National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing 102206, China
Funds: We thank Dr Ligang Wu for providing us with the luciferase reporters for Ago2 slicer activity test. This work was supported by the National Natural Science Foundation of China (31401202).
Received Date: 2020-10-25
Accepted Date:2021-03-13
Rev Recd Date:2021-03-09
Publish Date:2021-04-20
Abstract
Abstract
Repair of DNA double-strand break (DSB) is critical for the maintenance of genome integrity. A class of DSB-induced small RNAs (diRNAs) has been shown to play an important role in DSB repair. In humans, diRNAs 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). S672A mutation of Ago2 leads to significant reduction in Rad51 foci formation and HR efficiency. We further show that defective association of Ago2 S672A variant with DSB sites, instead of defects in diRNA 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.Keywords: Ago2,
diRNA,
DNA repair,
Phosphorylation,
Small RNA
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