Germline Mutations in BAP1 Impair Its Function in DNA Double-Strand Break Repair
Copyright policy )Germline Mutations in BAP1 Impair Its Function in DNA Double-Strand Break Repair
Abstract The BRCA1-associated deubiquitylase BAP1 is mutated in several cancers, most notably mesothelioma and melanoma, where it is thought to promote oncogenesis. In this study, we present evidence that BAP1 functions as part of the DNA damage response (DDR). We found that BAP1 mediates rapid poly(ADP-ribose)-dependent recruitment of the polycomb deubiquitylase complex PR-DUB to sites of DNA damage. Furthermore, we identified BAP1 as a phosphorylation target for the DDR kinase ATM. Functionally, BAP1 promoted repair of DNA double-strand breaks, enhancing cell survival after DNA damage. Our results highlight the importance of ubiquitin turnover at sites of DNA damage, and they provide a mechanism to account for the tumor-suppressive function of BAP1. Cancer Res; 74(16); 4282–94. ©2014 AACR.
- Cairo University Egypt
- University of Alberta Canada
- Université Laval Canada
Osteosarcoma, Lung Neoplasms, DNA Repair, Tumor Suppressor Proteins, Bone Neoplasms, DNA, Neoplasm, Transfection, Cell Line, Tumor, Humans, DNA Breaks, Double-Stranded, Ubiquitin Thiolesterase, Germ-Line Mutation
Osteosarcoma, Lung Neoplasms, DNA Repair, Tumor Suppressor Proteins, Bone Neoplasms, DNA, Neoplasm, Transfection, Cell Line, Tumor, Humans, DNA Breaks, Double-Stranded, Ubiquitin Thiolesterase, Germ-Line Mutation
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