Research in our laboratory represents a consistent effort to understand how enzymes, and transcriptional and translational regulators interact with nucleic acids to affect cellular development and disease outcome. Amongst the enzymes we are studying are eukaryotic translesion DNA synthesis polymerases (Poln Poll, Polk and Rev1), which have the ability to replicate through DNA lesions that would otherwise stall the replication machinery. Mutations in Poln, for example, cause of variant form of xeroderma pigmentosum (XPV), a heritable, cancer-prone syndrome in humans. We are also deeply interested in questions of specificity and how proteins translocate on DNA to select the correct sequence from the sea of nonspecific sequences in a cell. Here, our effort is focused on restriction endonucleases such as BamHI, and, we have, for example, determined structures of BamHI at almost every stage of its catalytic pathway. The work on transcription is motivated by questions of specificity in vivo, as they relate to homeotic proteins; and, in understanding the innate cellular response to viral infection mediated by interferon regulatory factors (IRFs). Transcription is, however, only one mechanism for regulating gene expression. Translational regulation plays an equally important role, but an understanding of the underlying mechanisms has been hindered by the lack of structural data. As such, we are exploring the structures of several key proteins that control mRNA translation during early fly development.