BRCA2 DNA repair associated | Elisa - Clia - Antibody - Protein

Background

BRCA2 (Breast Cancer 2) is a crucial gene associated with DNA repair and genomic stability. Located on chromosome 13q13.1, the BRCA2 gene was identified due to its significant role in hereditary breast and ovarian cancers. Similar to BRCA1, mutations in BRCA2 lead to a markedly increased risk of breast and ovarian cancer, with male carriers also at an elevated risk for breast and prostate cancers. The BRCA2 protein, encoded by this gene, is involved in the repair of DNA double-strand breaks through homologous recombination, an error-free repair process essential for maintaining genomic integrity. Mutations in BRCA2 disrupt this repair mechanism, leading to increased genomic instability and the accumulation of mutations that drive cancer development.

BRCA2’s role in DNA repair is critical not only for preventing cancer but also for understanding cancer biology and developing therapeutic interventions. The gene is composed of 27 exons and encodes a protein of 3418 amino acids. This protein directly interacts with RAD51, a recombinase protein essential for the homologous recombination repair process. The importance of BRCA2 extends beyond breast and ovarian cancers; it is also implicated in other malignancies, such as pancreatic cancer, melanoma, and various gastrointestinal cancers.

Protein Structure

The BRCA2 protein is characterized by several functional domains:

• BRC Repeats: Eight BRC repeats located in the central region of the protein are crucial for binding RAD51, facilitating its recruitment and function in homologous recombination.
• DNA-Binding Domain (DBD): This domain interacts with single-stranded and double-stranded DNA, playing a pivotal role in the DNA repair process.
• C-terminal Domain: Contains a nuclear localization signal and is involved in regulating the subcellular localization of BRCA2.

Classification and Subtypes

BRCA2 is classified as a tumor suppressor gene, critical for DNA damage response and repair mechanisms. The gene does not have subtypes, but mutations in BRCA2 are numerous and diverse, with over 2000 different variants reported. These mutations range from small insertions and deletions to large rearrangements, each affecting the gene’s function and cancer risk differently.

Function and Biological Significance

BRCA2 is essential for several key cellular processes:

• DNA Repair: Facilitates homologous recombination repair by recruiting and stabilizing RAD51 at the site of DNA double-strand breaks.
• Genomic Stability: Maintains chromosomal integrity by ensuring accurate DNA repair, thereby preventing the accumulation of genetic alterations.
• Cell Cycle Regulation: Involved in cell cycle checkpoints, particularly the S and G2/M phases, preventing the progression of cells with damaged DNA.
• Tumor Suppression: Acts as a tumor suppressor by maintaining genomic stability and preventing the development of cancerous mutations.

Clinical Issues

Mutations in BRCA2 significantly increase the risk of several cancers:

• Breast Cancer: Carriers have up to a 70% lifetime risk.
• Ovarian Cancer: Female carriers have a 10-30% lifetime risk.
• Male Breast Cancer: Elevated risk for male carriers.
• Prostate Cancer: Increased risk in male carriers.
• Other Cancers: Higher risks for pancreatic cancer, melanoma, and various gastrointestinal cancers.

Genetic testing for BRCA2 mutations is vital for risk assessment and management in individuals with a family history of these cancers. It informs decisions on preventive measures, such as prophylactic surgeries, chemoprevention, and enhanced surveillance strategies.

Summary

BRCA2 is a fundamental gene in DNA repair and genomic stability. Its role in homologous recombination repair is crucial for preventing cancer by maintaining chromosomal integrity. Mutations in BRCA2 lead to increased risks of various cancers, making it a critical focus for genetic testing and targeted therapies. Understanding BRCA2's function and the impact of its mutations is essential for developing effective cancer prevention and treatment strategies.