Mutations in the human BRCA2 gene are associated with susceptibility to early-onset breast cancer, but it is unclear how the wild-type BRCA2 protein works. In the July 17 Proceedings of the National Academy of Sciences, Xia et al. describe investigation of the role of BRCA2 in DNA repair (Proc Natl Acad Sci USA 2001, 98:8644-8649). They expressed BRCA2 in Capan-1 carcinoma cells, the only human cell line that has non-functional BRCA2. BRCA2 expression increased homologous recombination ten-fold,
Jonathan Weitzman(jonathanweitzman@hotmail.com)
Mutations in the human BRCA2 gene are associated with susceptibility to early-onset breast cancer, but it is unclear how the wild-type BRCA2 protein works. In the July 17 Proceedings of the National Academy of Sciences, Xia et al. describe investigation of the role of BRCA2 in DNA repair (Proc Natl Acad Sci USA 2001, 98:8644-8649). They expressed BRCA2 in Capan-1 carcinoma cells, the only human cell line that has non-functional BRCA2. BRCA2 expression increased homologous recombination ten-fold, and required interaction with the Rad51 protein. This homologous recombination increase resulted in increased resistance to ionizing radiation. BRCA2 expression had no effect on non-homologous end joining (NHEJ), another double-strand-break repair pathway. Thus, BRCA2 regulation of homologous recombination ensures the repair of damaged DNA to maintain genome integrity.
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