The BRCA2 gene is mutated in many familial and sporadic breast and ovarian cancers, making it an important cancer suppressor. BRCA2 has been long known to function together with RAD51 in DNA break repair by homologous recombination, but more recent evidence additionally implicated BRCA2-RAD51 in the protection of newly replicated DNA against unscheduled degradation. The Cejka laboratory used biochemical methods to show that RAD51 protects DNA against degradation upon its binding to double-stranded DNA. Binding of RAD51 to double-stranded DNA stands in contrast to single-stranded DNA, which is necessary for homologous recombination.
BRCA2 is known to affect the binding of RAD51 to DNA. The Cejka laboratory demonstrated that BRCA2 regions that stabilize RAD51 on ssDNA are not needed for DNA protection against nucleases, while the C-terminal BRCA2 region that promotes both single- and double-stranded DNA binding by RAD51 is effective in strengthening the capacity of RAD51 to prevent nucleolytic action. The results overall indicate a potential physiological function of double-stranded DNA binding by RAD51. The study was recently published in Molecular Cell. Dr. Swagata Halder, now assistant professor at Plaksha University (India) is the first authors of the study, assisted by multiple members of the Cejka laboratory including Dr. Aurore Sanchez.