https://scholars.lib.ntu.edu.tw/handle/123456789/611188
標題: | ASTE1 promotes shieldin-complex-mediated DNA repair by attenuating end resection | 作者: | Zhao, Fei Kim, Wootae Gao, Huanyao Liu, Chao Zhang, Yong Chen, Yuping Deng, Min Zhou, Qin Huang, Jinzhou Hu, Qi SHIH-HSUN CHEN Nowsheen, Somaira |
公開日期: | 八月-2021 | 出版社: | Nature Research | 卷: | 23 | 期: | 8 | 起(迄)頁: | 894-904 | 來源出版物: | Nature Cell Biology | 摘要: | The shieldin complex functions as the downstream effector of 53BP1–RIF1 to promote DNA double-strand break end-joining by restricting end resection. The SHLD2 subunit binds to single-stranded DNA ends and blocks end resection through OB-fold domains. Besides blocking end resection, it is unclear how the shieldin complex processes SHLD2-bound single-stranded DNA and promotes non-homologous end-joining. Here, we identify a downstream effector of the shieldin complex, ASTE1, as a structure-specific DNA endonuclease that specifically cleaves single-stranded DNA and 3′ overhang DNA. ASTE1 localizes to DNA damage sites in a shieldin-dependent manner. Loss of ASTE1 impairs non-homologous end-joining, leads to hyper-resection and causes defective immunoglobulin class switch recombination. ASTE1 deficiency also causes resistance to poly(ADP-ribose) polymerase inhibitors in BRCA1-deficient cells owing to restoration of homologous recombination. These findings suggest that ASTE1-mediated 3′ single-stranded DNA end cleavage contributes to the control of DSB repair choice by 53BP1, RIF1 and shieldin. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/611188 | ISSN: | 14657392 | DOI: | 10.1038/s41556-021-00723-9 |
顯示於: | 生化科學研究所 |
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