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Gene Regulation and Signaling

Regulation of gene expression is an intricate process involving DNA replication, transcription and translation. Central to each step in this tightly controlled net of operations are assemblies between nucleic acids and proteins. Likewise, signaling events within the cell involve an elaborate interplay between proteins undergoing specific modifications, used as “on/off” switches. Our laboratory uses a combination of approaches to physically map and biophysically and structurally characterize these interactions.

In simple, prototypic systems such as viruses, proteins necessary for replication are responsible for recognition of the origin sequences, unwinding of the nucleic acid, and initiation of replication by recruitment of factors (including polymerase) that assemble at the replication fork. We have investigated rolling circle replication, the paradigm for autonomously replicating nucleic acid elements, and have structurally elucidated essential components of the replisome, such as the Rep protein. In addition protein-protein signaling involving phosphorylation is another area of special focus.