The faithful transmission of genetic information is an important biological imperative. To carry out this function, organisms have evolved processes to replicate their genomes and defend them from attack. We study two important mechanisms associated with these processes, DNA replication and nucleotide excision repair. My group applies X-ray crystallography, supplemented with electron microscopy, to understand these long-standing problems in DNA biology. We also use biochemical studies to inform these approaches and follow up on the resulting insights.