Findings shed light on why BRCA2 mutations predispose to breast cancer

A site on BRCA2 called serine 3291 appears to regulate the activity of RAD51, a recombination protein involved in DNA repair, new research shows. This finding provides new insight into why deletions of this BRCA2 region predispose to breast cancer and promote radiation sensitivity.

Previous reports have suggested that BRCA2 mutations lead to tumor formation by inducing defective DNA repair. Still, the details of this process were unclear.In the present study, reported in the March 31st issue of Nature, Dr. Stephen C. West, from Cancer Research UK in South Mimms, and colleagues show that serine 3291 can exist in two states: phosphorylated or unphosphorylated. In the phosphorylated state, serine 3291 prevents BRCA2 from interacting with RAD51. During the cell cycle, phosphorylation of serine 3291 is low during S phase, but increases as mitosis approaches. “Although it is unlikely that S3291 phosphorylation provides the only regulatory mechanism that controls recombinase activity, this model provides a simple explanation for the activation of RAD51 in response to DNA-damaging agents,” the authors state. (Source: Nature 2005;434:598-604: Reuters Health: Oncolink: April 2005.)