BRCA1 Vital to Gene Repair in Cancer

Genetic changes to BRCA1 predicts higher risk of breast and ovarian cancers.

Researchers in a recent study were able to understand the vital role BRCA1 plays in gene repair.

Changes in the BRCA1 gene are associated with an increased risk of developing breast or ovarian cancer. If confirmed by other studies, patients with genetic changes in BRCA1 could be identified as having a higher risk of developing these cancers, according to the study published in Nature Structural & Molecular Biology.

BRCA1 produces a protein that attaches ubiquitin to other proteins. Ubiquitin helps regulate different bodily processes.

Researchers in the current study have found that the attachment of ubiquitin by the BRCA1 gene (ubiquitin ligase activity) is needed for homologous recombination, which is a specific type of error-free DNA repair.

Mutations that lead to cancer result from a lack of this type of DNA repair. Researchers found that cells without the BRCA1 ubiquitin ligase activity were sensitive to DNA damaging agents that required homologous recombination for repair, according to the study.

"We know that loss of BRCA1 is associated with a high risk of breast cancer, so getting to grips with understanding this gene has been a major aim of breast cancer research,” said lead study author Jo Morris, PhD, BSc. “This study may explain why some cancer predisposing mutations are found in the front part of the BRCA1 gene, the part that allows it to function as an ubiquitin ligase."

Researchers found that a partner protein, BARD1, assisted BRCA1 in performing the ubiquitin attachment role. Investigators then used changed versions of BARD1 and untouched versions of BRCA1 to identify the function of BRCA1.

According to the study, this is needed for cell response and proper DNA repair.

"Our finding that BRCA1 has several independent functions in DNA repair has implications for treatment. Clinicians are currently worried that breast cancer patients with low or absent BRCA1 may become resistant to therapeutic agents such as Olaparib,” Dr Morris concluded. “Our data show that cancer cells without BRCA1 have more than one ‘Achilles heel,’ and so there are more ways to target cancers and therefore to prevent tumors becoming resistant to treatment."