Genetic information is continuously exposed to endogenous and exogenous factors damaging DNA such as ultra-violet light, ionizing radiation, alkylating or crosslinking agents. To repair and maintain genetic integrity, various sophisticated pathways have evolved to cope with different types of DNA lesions. We are interested in understanding the molecular mechanisms that underlie DNA processing in DNA repair and how different repair pathways are interconnected. We combine hybrid methods in structural biology with biochemical approaches to study the action of structure-selective nucleases (cutting) during homologous recombination and how the DNA replication machinery bypasses DNA lesions (synthesis).

The talk will explain structural insights into human Holliday junction resolvase GEN1 and our efforts to reconstitute a minimal translesion DNA synthesis complex.