BRCA1 (BReast CAncer gene one) is located in chromosome 17q21, while BRCA2 (BReast CAncer gene two) is located in chromosome 13q12.3. These genes play a significant role in breast cancer because mutations in these two genes account for up to 10% of all breast cancer cases. Hundreds of cancer-associated mutations in BRCA1/2 BRCA 1 2 have been documented, and they are not only specific to breast and ovarian cancer.

Both BRCA1 and BRCA2 are tumor suppressor genes and subclassified as caretakers. BRCA1 is involved in both the nonhomologous end joining repair and homologous recombination, while BRCA2 is only involved in homologous recombination. BRCA1 and BRCA2 work with other important proteins to arrest the cell cycle division and perform DNA repair (commonly repairing double-stranded breaks), such as KU proteins that are involved in nonhomologous end joining and Rad51 proteins that are involved in homologous recombination. (Figure 1)

Steps that occur in two different double stranded DNA repair strategies: non-homologous end joining and homologous recombination. In non-homologous end joining, or NHEJ, the recognition step occurs when KU70 slash KU80 proteins recognize a break and recruit DNA-dependent protein-kinase catalytic subunit to the break site. The next step in NHEJ is end processing, which involves MRN complex and artemis nuclease. These factors work together to create blunt DNA ends. In the final step, ligation, DNA ligase 4 and a ligation factor join the two blunt DNA ends together, repairing the break. The other process shown in the digram is homologous recombination, or HR. In the first step of HR, MRN and ATM complexes are involved in end resection at the double stranded break site. Next, the proteins RAD51 and RPA are involved in strand invasion, DNA synthesis, and resolution. In these steps DNA from the homologous and intact region on a sister chromatid is used as a template to repair the double stranded break.

Figure 1. There are two separate pathways to repair double-strand DNA breaks: nonhomologous end joining and homologous recombination.