Dr. Sparks focuses on a protein complex called the eukaryotic replisome, which replicates cellular DNA during cell division. He is studying how the replisome handles persistent bulky DNA lesions that block the progression of the replicative helicase enzyme and how cells repair covalent DNA-protein cross-links (DPCs). DPCs are generated by formaldehyde and other endogenous metabolites and environmental mutagens and are almost certainly important for cancer etiology. Genome instability is a hallmark of all cancers, and mechanisms that either prevent or enhance this instability have many implications for cancer biology.