Ubiquitylation of Ku80 by RNF126 promotes completion of nonhomologous end joining-mediated DNA repair

Noriko Ishida, Tadashi Nakagawa, Shun Ichiro Iemura, Akira Yasui, Hiroki Shima, Yasutake Katoh, Yuko Nagasawa, Toru Natsume, Kazuhiko Igarashi, Keiko Nakayama

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20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere00347
JournalMolecular and cellular biology
Volume37
Issue number4
DOIs
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Ishida, N., Nakagawa, T., Iemura, S. I., Yasui, A., Shima, H., Katoh, Y., Nagasawa, Y., Natsume, T., Igarashi, K., & Nakayama, K. (2017). Ubiquitylation of Ku80 by RNF126 promotes completion of nonhomologous end joining-mediated DNA repair. Molecular and cellular biology, 37(4), [e00347]. https://doi.org/10.1128/MCB.00347-16