BRCA1 is a gene whose name is among the most familiar to the general public of all genes – for the unfortunate reason that mutations of BRCA1 are associated with significantly increased hereditary risk for breast cancer (as the name suggests). Strangely, however, it’s still not known exactly how mutations of BRCA1 confer this greater risk for cancer. But recent research has narrowed down the possibilities.
The protein that the gene codes for, BRCA1, is a fairly long chain of 1863 amino acids. BRCA1 is known to be involved in repair of damaged DNA. If BRCA1 is defective (due to a gene mutation), the failure to properly repair DNA (which can become damaged for many possible reasons) can lead to a cell becoming cancerous.
Previous research has identified around 1500 different mutations of BRCA1 associated with cancer risk. But most of these mutations directly affect the amino acids of only two different regions of BRCA1. Every protein has an amine group at one end of its chain and a carboxyl group at the other end. One of the two regions in which mutations lead to cancer is at the amino end and is called the “RING domain”. The other region, near the carboxyl end, is called BRCT (BRCA1 carboxyl-terminal tandem repeats).
The RING domain is known to have a role in the process that attaches a marker called ubiquitin to a protein in order to identify the protein as ready for recycling. The BRCT region is associated with the process of protein phosphorylation, which is a key element of chemical signaling within cells. What hasn’t been known is what aspects of DNA repair are disrupted by defects in one or both of these regions.