InterPro domain: IPR015525

The breast cancer type 2 susceptibility protein (BRCA2) is a breast tumour suppressor involved in double-strand break repair and/or homologous recombination [ 1 ]. BRCA2 gene expression is regulated in a cell-cycle dependent manner and peak expression of BRCA2 mRNA occurring in S phase, suggesting BRCA2 may participate in regulating cell proliferation. BRCA2, and related protein BRCA1, have transcriptional activation potential and the two proteins are associated with the activation of double-strand break repair and/or homologous recombination. The two proteins have been shown to coexist and colocalize in a biochemical complex. BRCA2 has a number of 39 amino acid repeats [ 2 ] that are critical for binding to RAD51 (a key protein in DNA recombinational repair) and resistance to methyl methanesulphonate treatment [ 3 , 4 , 5 ]. There are eight repeats in BRCA2 designated as BRC1 to BRC8. BRC1, BRC2, BRC3, BRC4, BRC7, and BRC8 have high sequence identity and bind to Rad51, whereas BRC5 and BRC6 are less well conserved and are unable to bind Rad51 [ 6 ]. 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.

Mutations in BRCA1 and BRCA2 have been linked to an elevated risk of young onset breast cancer and confer a high risk of the disease through a dominantly inherited fashion [ 7 ]. BRCA2 mutations are typically microdeletions.

Homologues exist in plants: the BRCA2A and BRCA2B proteins from Arabidopsis thaliana are required for repair of breaks in double-stranded DNA and homologous recombination and in the prophase stage of meiosis are required for formation of RAD51 and DMC1 foci in males [ 8 ].

1. Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature 420, 287-93
2. Internal repeats in the BRCA2 protein sequence. Nat. Genet. 13, 22-3
3. RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J. Biol. Chem. 272, 31941-4
4. 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
5. The BRCA2 gene product functionally interacts with p53 and RAD51. Proc. Natl. Acad. Sci. U.S.A. 95, 13869-74
6. 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
7. Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions: implications for prediction of pathogenicity. Hum. Mutat. 31, E1484-505
8. BRCA2 is a mediator of RAD51- and DMC1-facilitated homologous recombination in Arabidopsis thaliana. New Phytol. 193, 364-75