Mutations altering the DNA binding domains of the human RAD52 protein exert distinct effects on homologous recombination repair in Saccharomyces cerevisiae.

RAD52 is a conserved member of the homologous recombination repair (HRR) apparatus from yeast to humans. Mutating conserved amino acids in the internal and external DNA binding domains of the human RAD52 protein (HsRAD52) has discrete effects in vitro. Previous studies have shown that HsRAD52 supports multiple mechanisms of HRR in budding yeast, suggesting the utility of this model system for exploring the correspondence between losses of HsRAD52 function in vitro and their impact in vivo. We report that disrupting the internal and external DNA binding domains of HsRAD52 produced distinct effects on the repair of genomic DNA double-strand breaks (DSB) by conservative and non-conservative HRR in budding yeast, suggesting that these domains contribute to separate mechanisms in vivo. The further elucidation of the effects of perturbations in the structure and biochemical function of HsRAD52 in living systems will provide new insight into its ability to support DSB repair, cancer susceptibility as well as new avenues for targeting HRR-deficient cancers.