We aim to understand how proteins recognize nucleic acids, leading to cleavage, regulation of transcription/translation, and replication. For example, we have determined structures of endonuclease BamHI at almost every stage of its catalytic pathway. Together, these structures have helped to change our view of the conformational transitions that can occur when proteins bind to DNA. An increasing emphasis of our structural work on transcription is on complexes that underlie homeotic development and the cellular response to specific extracellular signals. Transcription is only one mechanism for regulating gene expression. Translational regulation plays an equally important role, particularly in early embryogenesis. Here our work is focused on proteins such as Pumilio and Smaug that repress the translation of hunchback and Nanos mRNAs in fly embryos. An exciting new direction in the lab is structural studies of DNA repair polymerases. These include DNA polymerase eta (Pol eta), mutations in which cause the cancer-prone variant form of xeroderma pigmentosum. Pol eta is thus the first DNA polymerase demonstrated to act as a tumor suppressor in humansProtein:Nucleic Acid Interactions