Attenuation of Human DMC1 Recombination Activities by Substitution of a Conserved Residue

Unrepaired DNA double strand breaks (DSB) are detrimental to the viability of the cell. The repair of DSBs can occur by a process called homologous recombination (HR). HR is used whenever the cell has a homologous template in the way of a homologous chromosome available. The process of HR during mitosis is different from meiotic HR. To initiate meiotic recombination, DSBs are formed and processed to allow proper chromosome segregation and ultimately genetic variation. Meiotic HR is mediated by the meiosis specific recombinase, DMC1. The DMC1 recombinase binds to the 3’ end of a newly resected DSB forming a nucleoprotein filament called the presynaptic filament. Once the presynaptic filament is formed, DMC1 can search for homology and invade the homologous chromosome creating a D-loop. The D-loop is extended through DNA synthesis using the homologous chromosome as a template for repair. The aim in this study was to characterize a novel mutation in human DMC1 modeled after a mutation in Arabidopsis thaliana that resulted in sterility. This mutation is in proximity to the two DNA binding sites. The results in this study suggest the mutation alters the DNA binding sites leading to defective D-loop formation. More studies are needed to confirm if other functions are hindered