Phosphorylation of Ago2 is required for its role in DNA double-strand break repair

• 作者: Xiaolu Hu Yan Li Tianfang Zhang Lin Li She Chen Xiaohong Wu Haijun Li Binjie Qi Zuobing Chen
• 来源期刊: 遗传学报
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: Original Research
• 页码范围: 333-340
• 页数: 8页
• 语种: 英文

摘要

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 un-explored.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.