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

Research output: Contribution to journalArticle

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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 - Jan 1 2017

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DNA End-Joining Repair
Ubiquitination
DNA Repair
Double-Stranded DNA Breaks
DNA
Ligases
Ubiquitin
Eukaryota
Lysine
Chromatin
Arginine
Enzymes
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Ishida, N., Nakagawa, T., Iemura, S. I., Yasui, A., Shima, H., Katoh, Y., ... 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

Ubiquitylation of Ku80 by RNF126 promotes completion of nonhomologous end joining-mediated DNA repair. / Ishida, Noriko; Nakagawa, Tadashi; Iemura, Shun Ichiro; Yasui, Akira; Shima, Hiroki; Katoh, Yasutake; Nagasawa, Yuko; Natsume, Toru; Igarashi, Kazuhiko; Nakayama, Keiko.

In: Molecular and cellular biology, Vol. 37, No. 4, e00347, 01.01.2017.

Research output: Contribution to journalArticle

Ishida, N, Nakagawa, T, Iemura, SI, 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, vol. 37, no. 4, e00347. https://doi.org/10.1128/MCB.00347-16
Ishida, Noriko ; Nakagawa, Tadashi ; Iemura, Shun Ichiro ; Yasui, Akira ; Shima, Hiroki ; Katoh, Yasutake ; Nagasawa, Yuko ; Natsume, Toru ; Igarashi, Kazuhiko ; Nakayama, Keiko. / Ubiquitylation of Ku80 by RNF126 promotes completion of nonhomologous end joining-mediated DNA repair. In: Molecular and cellular biology. 2017 ; Vol. 37, No. 4.
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