Meiotic recombination is initiated by DNA double-strand breaks (DSBs) generated by the topoisomerase-like Spo11 protein. We are studying the mechanism and regulation of Spo11-dependent DSB formation in the yeast S. cerevisiae, as well as examining the factors that dictate where Spo11 cleaves the DNA and that control the outcome of the recombination process.
Many aspects of meiotic recombination, such as its initiation via Spo11-generated DSBS, are highly conserved throughout evolution. We are examining the mechanisms that control the distribution of crossover recombination products along chromosomes, the factors that connect recombination with the development of specialized higher order chromosome structures, and the checkpoints that monitor the progression of recombination.
Topoisomerase poisons are important anti-cancer chemotherapeutic agents, but can also cause mutations that lead to cancer. In this project, we aim to elucidate how mammalian and yeast cells respond to and repair the DNA damage induced by these drugs.