First EM Pictures of BRCA2 Protein Show How It Works to Repair DNA

Scientists have taken pictures of the BRCA2 protein for the first time, showing how it works to repair damaged DNA. Mutations in the gene that encodes BRCA2 are well known for raising the risk of breast cancer and other cancers. Although the protein was known to be involved in DNA repair, its shape and mechanism have been unclear, making it impossible to target with therapies. Researchers at Imperial College London and the Cancer Research UK London Research Institute purified the protein and used electron microscopy to reveal its structure and how it interacts with other proteins and DNA. The results were published online on October 5, 2014 in Nature Structural and Molecular Biology. Approximately one in 1,000 people in the UK have a mutation in the BRCA2 gene. The lifetime risk of breast cancer for women with BRCA2 mutations is 40 to 85 per cent, depending on the mutation, compared with approximately 12 per cent for the general population. Many women who test positive for BRCA1 and BRCA2 mutations choose to undergo surgery to reduce their risk of breast cancer. Mutations can also raise the risk of other cancers, such as ovarian, prostate, and pancreatic cancer. The BRCA1 and BRCA2 genes encode proteins involved in DNA repair. The DNA in our cells undergoes damage thousands of times a day, caused by toxic chemicals, metabolic by-products, and ultraviolet radiation. Repair mechanisms correct most of this damage, but unrepaired damage can lead to cancer. The current study was led by Professor Xiaodong Zhang from the Department of Medicine at Imperial College London and Dr. Stephen West at the London Research Institute. "This study improves our understanding of a fundamental cause of cancer," said Professor Zhang, a Wellcome Trust Senior Investigator.
Login Or Register To Read Full Story