BRCA1 DNA repair associated | Elisa - Clia - Antibody - Protein

Background

BRCA1 (Breast Cancer 1) is a critical gene involved in maintaining genomic stability. Located on chromosome 17q21, BRCA1 was discovered due to its association with hereditary breast and ovarian cancers. Mutations in the BRCA1 gene significantly increase the risk of developing these cancers, with carriers having up to an 80% lifetime risk of breast cancer and a 40-60% risk of ovarian cancer. BRCA1 encodes a protein that plays a pivotal role in DNA repair, specifically in homologous recombination, a high-fidelity DNA repair process. The BRCA1 protein is also involved in cell cycle control, transcriptional regulation, and maintaining genomic integrity. Its role as a tumor suppressor gene is crucial, as it helps prevent the accumulation of genetic alterations that can lead to cancer.

Protein Structure

The BRCA1 protein consists of 1863 amino acids and has several functional domains:

• RING Domain: Located at the N-terminus, this domain mediates protein-protein interactions and is essential for the ubiquitin ligase activity of BRCA1, which tags damaged proteins for degradation.
• BRCT Domains: These C-terminal domains are crucial for phospho-protein binding and are involved in DNA repair, cell cycle checkpoint control, and transcription regulation.
• Coiled-coil Domain: This domain facilitates the interaction with PALB2, another protein essential for the homologous recombination repair process.
• Serine-Containing Domain: It interacts with several proteins involved in DNA damage response and repair.

Classification and Subtypes

BRCA1 belongs to the tumor suppressor gene class, specifically involved in DNA damage response and repair mechanisms. While BRCA1 itself does not have subtypes, mutations within the BRCA1 gene can be classified into thousands of distinct variants, each potentially influencing cancer risk differently.

Function and Biological Significance

BRCA1 plays multiple critical roles in cellular processes:

• DNA Repair: BRCA1 is integral to the repair of double-strand breaks through homologous recombination. It helps maintain genomic stability by facilitating accurate repair.
• Cell Cycle Regulation: BRCA1 is involved in cell cycle checkpoints, particularly the S-phase and G2/M transition, ensuring cells do not progress through the cycle with DNA damage.
• Transcriptional Regulation: BRCA1 regulates the expression of various genes involved in DNA repair and apoptosis.
• Ubiquitination: The RING domain of BRCA1 has ubiquitin ligase activity, tagging damaged proteins for degradation and thus playing a role in protein quality control.

Clinical Issues

Mutations in BRCA1 lead to a significantly increased risk of breast and ovarian cancers. These mutations can be inherited in an autosomal dominant manner, making genetic counseling and testing crucial for individuals with a family history of these cancers. BRCA1 mutations are also associated with increased risks for other cancers, including prostate and pancreatic cancer.

Summary

BRCA1 is a fundamental gene in maintaining genomic stability, involved in DNA repair, cell cycle regulation, and transcriptional control. Mutations in BRCA1 significantly elevate the risk of breast, ovarian, and other cancers due to the loss of its tumor suppressor functions. Understanding BRCA1's roles and mechanisms is vital for developing targeted therapies and preventive measures for those at high genetic risk. Genetic testing for BRCA1 mutations is an essential tool in personalized medicine, allowing for tailored surveillance and intervention strategies.