Repair of damaged DNA by homologous recombination and related pathways
We are primarily interested in the maintenance of genome stability. This subject is important from both basic research and human health standpoints. Accurate transmission of genetic information is essential to prevent mutagenesis, and DNA repair mechanisms were found to be essential for each round of DNA replication in human cells. Genome instability represents one of the hallmarks of cancer cells, and defects in DNA repair pathways are linked to a number of syndromes characterized by premature aging and predisposition to varieties of cancer. These processes are highly conserved in evolution, which underlines their fundamental importance in life, as well as justifies the use of model organisms (such as yeast S. cerevisiae) for their study. I would like to propose continue studying two ongoing projects in my laboratory. The first project is focused on the role of the human MMS22L-TONSL complex. The mechanism of activation of homologous recombination at ssDNA breaks, especially upon replication fork stalling is poorly understood. It was inferred that MMS22L-TONSL complex might play a role in the initiation of recombination-dependent repair. Indeed, we now have direct biochemical evidence that this is the case, and start to understand the underlying mechanisms. Our aim is to continue and extend the ongoing research. The second project concerns the yeast Dna2 helicase-nuclease. This is an essential and multifunction protein that acts in both DNA repair and replication. Our aim is to understand the role of Dna2 in the diverse cellular processes as well as how the enzyme's activity is regulated.