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Mol Cell Biol. 2017 Feb 1;37(4). pii: e00347-16. doi: 10.1128/MCB.00347-16. Print 2017 Feb 15.

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

Author information

1
Division of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.
2
Biomedical Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
3
Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Miyagi, Japan.
4
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
5
Division of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan nakayak2@med.tohoku.ac.jp.

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.

KEYWORDS:

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

PMID:
27895153
PMCID:
PMC5288581
DOI:
10.1128/MCB.00347-16
[Indexed for MEDLINE]
Free PMC Article

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