InterPro domain: IPR002093

The breast cancer type 2 susceptibility protein has a number of 39 amino acid repeats [ 1 ] that are critical for binding to RAD51 (a key protein in DNA recombinational repair) and resistance to methyl methanesulphonate treatment [ 2 , 3 , 4 ]. BRCA2 is a breast tumour suppressor with a potential function in the cellular response to DNA damage. At the cellular level, expressionis regulated in a cell-cycle dependent manner and peak expression of BRCA2 mRNA is found in S phase, suggesting BRCA2 may participate in regulating cell proliferation. There are eight repeats in BRCA2 designated as BRC1 to BRC8. BRC1, BRC2, BRC3, BRC4, BRC7, and BRC8 are highly conserved and bind to Rad51, whereas BRC5 and BRC6 are less well conserved and do not bind to Rad51 [ 5 ]. It has been suggested that BRCA2 plays a role in positioning Rad51 at the site of DNA repair or in removing Rad51 from DNA once repair has been completed.

1. Internal repeats in the BRCA2 protein sequence. Nat. Genet. 13, 22-3
2. RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J. Biol. Chem. 272, 31941-4
3. The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment. Proc. Natl. Acad. Sci. U.S.A. 95, 5287-92
4. The BRCA2 gene product functionally interacts with p53 and RAD51. Proc. Natl. Acad. Sci. U.S.A. 95, 13869-74
5. Expression of BRC repeats in breast cancer cells disrupts the BRCA2-Rad51 complex and leads to radiation hypersensitivity and loss of G(2)/M checkpoint control. J. Biol. Chem. 274, 32931-5