Aberrant DNA replication is one of the leading causes of mutations and chromosome rearrangements associated with several cancer related pathologies. At the same time, agents that stall or damage DNA replication forks are widely used for chemotherapy, in the attempt to selectively target highly proliferating cancer cells. Our group studies the mechanisms that operate in eukaryotic cells to maintain replication fork integrity upon chemical treatment with cancer chemotherapeutics.
We combine cellular, biochemical and structural approaches to define the molecular mechanisms used by eukaryotic ATP-dependent motor proteins to resolve potentially recombinogenic DNA structures that arise upon replication stress induction. We are particularly interested into the function of RecQ helicases in this process because of their central roles in the resolution of several DNA replication and repair intermediates.
The work in the laboratory is currently focused in two main areas: