BRCC3

BRCC3, also known as BRCA1/BRCA2-containing complex, subunit 3, is a protein that in humans is encoded by the BRCC3 gene. This protein is part of a larger enzyme complex known as the BRCA1-A complex, which is involved in the DNA repair process, specifically in the repair of DNA double-strand breaks through the homologous recombination pathway. BRCC3 has deubiquitinating enzyme activity and plays a critical role in the cellular response to DNA damage, helping to maintain genomic stability and prevent mutations that could lead to cancer.

Function

BRCC3 is a member of the JAMM/MPN+ metalloenzyme subfamily and exhibits deubiquitinase activity, which is essential for the repair of DNA double-strand breaks. It is involved in the processing of K63-linked polyubiquitin chains, a post-translational modification that signals the presence of DNA damage and recruits DNA repair proteins to the site of damage. By removing these ubiquitin chains, BRCC3 regulates the assembly and disassembly of DNA repair complexes, ensuring that repair processes are initiated and terminated correctly.

Clinical Significance

Mutations in the BRCC3 gene have been associated with an increased risk of developing certain types of cancer, including breast cancer and ovarian cancer, particularly in individuals with a family history of these diseases. This is due to the critical role of BRCC3 in DNA repair; when its function is compromised, DNA damage can accumulate, leading to genomic instability and the development of cancer. Additionally, BRCC3 has been studied as a potential target for cancer therapy, with the idea that inhibiting its activity could make cancer cells more susceptible to DNA-damaging agents used in chemotherapy.

Interaction

BRCC3 interacts with several other proteins within the BRCA1-A complex, including BRCA1, BRCA2, and RAD51, among others. These interactions are crucial for the recruitment of the complex to sites of DNA damage and for the efficient repair of DNA double-strand breaks.

See Also

• DNA repair
• Ubiquitin
• Homologous recombination
• Genomic instability
• Cancer

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