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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.

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


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.

[Indexed for MEDLINE]

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