Investigating the Biochemical Properties of a Novel Mutation, a194v, in Human RAD51

DNA double-strand breaks (DSB) are one of the most serious DNA lesions because improper repair of a DSB can lead to loss of heterozygosity, aneuploidy, and cancer. One of the primary pathways to repair DSBs is homologous recombination (HR). HR resects the DNA around the DSB and then uses homologous DNA as a template to restore the broken sequence. RAD51 has a vital function in this pathway by forming a nucleoprotein filament on a resected end of the DSB. The nucleoprotein filament searches for homology within the homologous DNA. Once homology is located, strand invasion followed by strand exchange occurs. Our research aims to characterize a novel mutation within RAD51 that was first identified in Arabidopsis thaliana Dmc1, which is the meiotic ortholog of RAD51. This mutation in A. thaliana Dmc1 was found to cause sterility in plants. We expect that this mutation in A. thaliana Dmc1 will also negatively affect the function of human RAD51 since the mutation is in a conserved sequence. Despite this expectation, we found that RAD51A194V had some degree of increased function in all areas we tested. The results from this work will provide insight into the function of this conserved region in the recombination activities of RAD51