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

Producción científica: Articlerevisión exhaustiva

26 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Número de artículo1577
PublicaciónNature communications
Volumen10
N.º1
DOI
EstadoPublished - dic 1 2019
Publicado de forma externa

ASJC Scopus subject areas

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

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