PALB2

PALB2

PALB2 (Partner and Localizer of BRCA2) is a protein that in humans is encoded by the PALB2 gene. It plays a critical role in DNA repair through its involvement in the homologous recombination (HR) pathway, a mechanism that repairs DNA double-strand breaks and interstrand crosslinks. PALB2 acts as a bridge between BRCA1 and BRCA2, two other key proteins involved in HR, facilitating the repair of DNA damage and maintaining genomic stability.

Mutations in the PALB2 gene are associated with an increased risk of developing certain cancers, most notably breast cancer and pancreatic cancer. These mutations can be inherited in an autosomal dominant manner, meaning a mutation in just one of the two copies of the gene a person has is sufficient to increase cancer risk. As such, PALB2 is considered a moderate-penetrance cancer susceptibility gene, similar to BRCA2.

Function

The PALB2 protein is essential for the recruitment of BRCA2 and RAD51, another protein crucial for DNA repair, to sites of DNA damage. By facilitating the formation of the BRCA1-PALB2-BRCA2 complex, PALB2 ensures the proper repair of DNA double-strand breaks through homologous recombination. This process is vital for the maintenance of genomic integrity and the prevention of tumorigenesis.

Clinical Significance

Mutations in PALB2 have been linked to familial breast cancer and, to a lesser extent, familial pancreatic cancer. Individuals with a pathogenic PALB2 mutation have a significantly increased lifetime risk of developing these cancers. Genetic testing for PALB2 mutations is often considered for individuals with a strong family history of breast or pancreatic cancer, especially if no mutations in BRCA1 or BRCA2 have been identified.

In addition to its role in cancer predisposition, research suggests that PALB2 mutations may influence the response to certain chemotherapy agents, particularly those that induce DNA damage, such as platinum-based chemotherapies. This has implications for personalized cancer treatment strategies.

Genetic Testing

Genetic testing for PALB2 mutations can provide important information for cancer risk assessment and management in families with a history of breast or pancreatic cancer. Positive identification of a mutation can lead to increased surveillance, preventive measures, and potentially targeted therapies for individuals at risk.

See Also

• BRCA1
• BRCA2
• Homologous recombination
• DNA repair
• Cancer genetics