泛素
细胞生物学
泛素连接酶
组蛋白
DNA损伤
DNA连接酶
DNA修复
同源重组
磷酸化
化学
DNA
生物
生物化学
基因
作者
Geun-Hyoung Ha,Jeong‐Seon Ji,Sung-Yoon Chae,Jihyun Park,Suhyeon Kim,Jin-Kwan Lee,Yonghyeon Kim,Sunwoo Min,Jeong-Min Park,Tae-Hong Kang,Ho Lee,Hyeseong Cho,Chang-Woo Lee
标识
DOI:10.1038/s41467-019-09641-9
摘要
Abstract DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and γH2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination.
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