BRCA1 the Gene and Protein
What is BRAC1
BRAC1 is gene associated with mutations which can cause malfunctions in cells resulting in cancer. It has a strong family history link and therefore any individual with a known tumor which is positive would have their family tested for the mutation also.
The mutation is not limited to women, men are not immune from the effects of the mutation. Men, even though lower numbers are recorded, can be susceptible to breast cancer. There is also evidence to suggest that BRAC1 mutation can lead to some lung cancers in men who smoke.
If found positive then some women have a difficult choice to make. It is very specific to the individual affected, they have had multiple children and a hysterectomy with associated complications may not phase them. Or they could be trying for a child and monitoring may be an option. There are numerous factors to consider and having a positive mutation in this gene does not necessarily mean cancer is a definite outcome, however the risk of developing cancer is higher if positive.
There is multiple literature available on the internet, and if you feel you are affected or in the process of undergoing tests, then your clinical team should be your first point of call for information and questions. There are also excellent references on charitable websites including Cancer Research.
This Hub is to provide some information on the science to the protein and the gene which are responsible in this mutation. The reason it is split into the gene and the protein is due to essentially genes provide a code for the body to make proteins, and the proteins perform the functions of the body.
Breast cancer early onset 1 gene or BRCA1 was first discovered in 1994 and is located on the long arm of chromosome 17 at band 21 (see image). Chromosomes have a long aspect and a short aspect and due to their nature have banding's. DNA and chromosome sequencing have allowed scientists to locate specific genes and where they are in our genome and thus the specificity of above.
It codes for a 200 KDa (measurement of molecular mass) protein, which consists of 1863 amino acids ('building blocks of life' making up DNA). The gene contains 22 coding exons (segments of DNA which get translated to make the protein) 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 damage 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 proteins essentially control the cell as it replicates and develops. These two BRCT domains have a sufficient mapped sequence identical to 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.