Cancer cells tend to display both mutational and chromosomal instability. In many instances, defects in genes encoding proteins involved in the maintenance of genomic integrity have been associated with either cancer predisposition syndromes or tumorigenesis in experimental animal models. A major aim of the Molecular Biology Program is to understand the relationship between disruption of the pathways that act to maintain the integrity of the genome and the occurrence of cancer. Our investigators use biochemical, molecular genetic, genetic, cell biological, and structural biological approaches to study many aspects of the maintenance of genomic integrity. For example, we are exploring DNA replication and its link to the cell cycle; mechanisms of DNA topoisomerases; mechanisms that underlie accurate transmission of chromosomes during cell division; the cellular response to DNA damage; the consequences of DNA damage, and the nonhomologous end-joining, homologous recombination, and replication restart pathways of DNA repair. Additional program strengths lie in the areas of regulation of gene expression and control of cell proliferation.