BRCA1 the Gene and Protein
BRCA1 or breast cancer early onset 1 gene, was first discovered in 1994 and is located on the long arm (q) of chromosome 17 at band 21 (see image). It codes for a 200 KDa protein, which consists of 1863 amino acids. The gene contains 22 coding exons (segments of DNA) and 2 non coding exons, with exon 11 coding for the majority of the protein (60% coding). The majority of these coding regions are organised into small exons normally lower than 100 base pairs, with exon 11 being organised into much larger numbers of base pairs.
The BRAC1 gene belongs to a class of genes known as tumour suppressors. These are responsible for maintaining genomic integrity and preventing uncontrolled cellular proliferation, in essence the development of cancer. Many different tissues express this gene including both testis and thymus, but its exact role in the cell is not fully understood. BRCA1 protein is thought to be directly involved in the repair of DNA damaged on exposure to certain elements such as Ultra violet (UV) light or strong chemical components such as hydroxyurea.
The structure of the protein BRCA1 is unknown having few identifiable features. Located at the N terminal region is a ring domain, these domains have been associated with many protein to protein interactions. Located at the C-terminal end of the protein are two 95 residue BRCT (BRCA1 C-terminal) domains. These domains are also found in other proteins that are involved in DNA repair and cell cycle regulation. These two BRCT domains have sufficient mapped sequence identity as the DNA repair protein XRCC1 BRCT domain. The crystal structure of this domain from this protein reveals a central, four stranded β-sheet surrounded by 3 α-helices. Contacts which mediate asymmetric dimerisation of the two BRCT domains of XRCC1 protein are predicted to involve residues of one of these α-helices located around the 4 β-pleated sheets. Mutations associated with mutations in BRCA1 are predicted to disrupt the stability or folding of the BRCT domain, this would be consistent with the effects of protein function.