Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks

Geun Hyoung Ha, Jae Hoon Ji, Sunyoung 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

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Article number1577
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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