BCRA2 involved in DNA repair

New images have revealed how BRCA2 works to repair damaged DNA. The protein was known to be involved in DNA repair, but its shape and mechanism have remained elusive. Electron microscopy has revealed not only the structure but how it interacts with other proteins and DNA. BRCA2 – along with BRCA1 – encode proteins involved in DNA repair. DNA can become damaged by toxic chemicals, metabolic by-products and ultraviolet radiation – if unrepaired this damage can lead to cancer. “This study improves  our understanding of a fundamental cause of cancer,” said Professor Xiaodong Zhang from Imperial College London, who co-led the study with Dr Stephen West at the London Research Institute. “It is our first view of how the protein looks and how it works, and it gives us a platform to design new experiments to probe its mechanism in greater detail.” BRCA2 proteins work in pairs, which researchers found surprising since it is one of the largest proteins in the cell. It works with RAD51 helping it to assemble on strands of broken DNA and form filaments. The RAD51 filaments then search for matching strands of DNA in order to repair the break. The findings – published in Nature Structural and Molecular Biology ­ – reveal that each pair of BRCA2 proteins binds two sets of RAD51 that run in opposite directions, allowing it to work on broken strands of DNA pointing in either direction. They also show that BRCA2 helps RAD51 form short filaments at multiple sites along the DNA, which scientists presume is to increase the efficiency of establishing longer filaments required to search for matching strands. “Once we have added more detail to the picture, we can design ways to correct defects in BRCA2 and help cells repair DNA more effectively to prevent cancer,” said Zhang. “We can also think about how to make the repair process less effective in cancer cells, so that they die.” Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor