Send to

Choose Destination
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

Division of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.
Biomedical Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Miyagi, Japan.
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Division of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan


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.


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

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center