| First Author | Ha GH | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 1577 |
| PubMed ID | 30952868 | Mgi Jnum | J:274532 |
| Mgi Id | MGI:6286973 | Doi | 10.1038/s41467-019-09641-9 |
| Citation | Ha GH, et al. (2019) Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks. Nat Commun 10(1):1577 |
| abstractText | 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 gammaH2AX-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. |
