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Nat Cell Biol. 2015 Nov;17(11):1446-57. doi: 10.1038/ncb3259. Epub 2015 Oct 26.

The RNF138 E3 ligase displaces Ku to promote DNA end resection and regulate DNA repair pathway choice.

Author information

1
Departments of Oncology and Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, 11560 University Avenue Edmonton, Alberta T6G 1Z2, Canada.
2
Biophysics Department, Faculty of Science, Cairo University, 12613 Giza, Egypt.
3
CHU de Québec Research Center, CHUL Pavilion, Oncology Axis, 2705 boul. Laurier Québec city, Québec G1V 4G2, Canada.
4
Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Québec City, Québec G1V 0A6, Canada.
5
Genome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Axis, 9 McMahon Québec City, Québec G1R 2J6, Canada.

Abstract

DNA double-strand breaks (DSBs) are repaired mainly by non-homologous end joining or homologous recombination (HR). Cell cycle stage and DNA end resection are believed to regulate the commitment to HR repair. Here we identify RNF138 as a ubiquitin E3 ligase that regulates the HR pathway. RNF138 is recruited to DNA damage sites through zinc fingers that have a strong preference for DNA with 5'- or 3'-single-stranded overhangs. RNF138 stimulates DNA end resection and promotes ATR-dependent signalling and DSB repair by HR, thereby contributing to cell survival on exposure to DSB-inducing agents. Finally, we establish that RNF138-dependent Ku removal from DNA breaks is one mechanism whereby RNF138 can promote HR. These results establish RNF138 as an important regulator of DSB repair pathway choice.

PMID:
26502055
DOI:
10.1038/ncb3259
[Indexed for MEDLINE]

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