Ubiquitylation of Ku80 by RNF126 Promotes Completion of Nonhomologous End Joining-Mediated DNA Repair

作者：Ishida Noriko; Nakagawa Tadashi^*; Iemura Shun Ichiro; Yasui Akira; Shima Hiroki; Katoh Yasutake; Nagasawa Yuko; Natsume Toru; Igarashi Kazuhiko; Nakayama Keiko

来源：Molecular and Cellular Biology, 2017, 37(4).

DOI：10.1128/MCB.00347-16

• DNA repair
• Ku80
• RNF126
• nonhomologous end joining (NHEJ)
• ubiquitylation

Repair of damaged DNA is critical for maintenance of genetic information. In eukaryotes, DNA double-strand breaks (DSBs) are recognized by the Ku70-Ku80 heterodimer, which then recruits proteins that mediate repair by nonhomologous end joining (NHEJ). Prolonged retention of Ku70/80 at DSBs prevents completion of repair, however, with ubiquitylation of Ku80 having been implicated in Ku70/80 dissociation from DNA. Here, we identify RNF126 as a ubiquitin ligase that is recruited to DSBs and ubiquitylates Ku80, with UBE2D3 serving as an E2 enzyme. Knockdown of RNF126 prevented Ku70/80 dissociation from DSBs and inhibited break repair. Attenuation of Ku80 ubiquitylation by replacement of ubiquitylation site lysines with arginine residues delayed Ku70/80 release from chromatin after DSB induction by genotoxic insults. Together, our data indicate that RNF126 is a novel regulator of NHEJ that promotes completion of DNA repair by ubiquitylating Ku80 and releasing Ku70/80 from damaged DNA.

• 出版日期2017-2