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

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 ?H2AX-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.
Mesh Terms:
Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins, Cell Line, Tumor, DNA Breaks, Double-Stranded, DNA Repair, Humans, Nuclear Proteins, Ubiquitin-Protein Ligases, Ubiquitination
Nat Commun
Date: Dec. 05, 2018
Download Curated Data For This Publication
219838
Switch View:
  • Interactions 9