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BRCA2 Gene Interactions

By Dr Ananya Mandal, MD

The BRCA1 and BRCA2 genes code for important tumor suppressor proteins. Also known of as the breast cancer type 2 susceptibility protein, BRCA2 is directly involved in the repair of damaged DNA.

Mutations in BRCA1 and BRCA2 are believed to be responsible for most hereditary breast cancers, which account for 5% to 10% of all breast cancer cases. Researchers have found over 800 mutations in the BRCA2 gene and many of these are associated with an increased risk for breast cancer. In around 52% of families in which four or more individuals have breast cancer, inherited mutations in BRCA1 are to blame and around 32% are due to BRCA2 mutations.

The BRCA2 gene is composed of 27 exons and codes for a 384-kDa protein. The gene has eight repetitive units and a potential nuclear localization in its C-terminus. There is a putative transcriptional activation domain in exon 3, meaning the gene plays a role in the regulation of gene expression. There is also evidence of the role of BRCA2 in DNA repair.

BRCA2, p53 gene and RAD51

Studies in vivo have shown that the BRCA2 protein forms complexes with the DNA repair protein RAD51 and with the tumor suppressor protein p53. Other studies have also shown that RAD51 interacts with p53. In addition, researchers have demonstrated that exogenous BRCA2 expression in tumor cells prevents the transcriptional activity of p53 while the co-expression of RAD51 increases the inhibitory effects of BRCA2.

Together, these findings show that BRCA2 interacts with these two important contributors to cell cycle control and DNA repair in order to maintain DNA integrity.

Reviewed by , BSc

Further Reading

Last Updated: Feb 25, 2014

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