Mouse Breast Cancer Susceptibility Protein 2 (BRCA2) Protein

Background

BRCA2 is a tumor suppressor protein that plays a pivotal role in maintaining genomic stability by facilitating the repair of DNA double-strand breaks through homologous recombination. It interacts with RAD51, a recombinase protein, to mediate the precise alignment and strand exchange during DNA repair. Structurally, BRCA2 contains eight BRC repeats that directly bind RAD51 and a DNA-binding domain that targets damaged DNA regions. Mutations in the BRCA2 gene are strongly associated with an increased risk of hereditary breast, ovarian, and other cancers, such as pancreatic and prostate cancer. These mutations often lead to truncated or dysfunctional proteins, resulting in impaired DNA repair and genomic instability, which drives tumorigenesis. Beyond its role in DNA repair, BRCA2 is also implicated in cell cycle regulation and replication fork protection. BRCA2 deficiency is therapeutically targeted using PARP inhibitors, exploiting synthetic lethality to selectively kill BRCA2-mutant cancer cells while sparing normal cells. This approach has revolutionized treatment options for BRCA2-associated cancers, emphasizing its clinical significance.