Molecular determinants of the BRC Repeats - RAD51 recognition

Homologous recombination (HR) is a key pathway for error-free repair of DNA double-strand breaks[1,2]. The central RAD51 and BRCA2 interaction remains yet incompletely characterized[1,2]. BRCA2 interacts with RAD51 through eight short BRC repeats, but structural information is only available for the RAD51–BRC4 complex, leaving the role of other repeats unclear. Indirect biochemical data suggest BRC1–4 can inhibit RAD51 DNA binding while BRC5–8 promote RAD51–DNA interaction, implying distinct functions during HR[3]. Nevertheless, no direct biophysical data are currently available on the individual contributions of the BRC repeats to RAD51 nuclear recruitment, a crucial step in HR[4]. To address this gap, we combined computational approaches, biophysical experiments, and integrative structural biology[5]. Starting with assessing the correlation between the binding affinities of individual BRC repeats and their impact on RAD51 binding and disassembly, our investigation extends to larger BRCA2 truncations, offering unprecedented insights into the molecular determinants of RAD51 recognition[5].