David Setzer

Professor of Biological Sciences

PhD, 1981 Stanford University

setzerd@missouri.edu
573-882-6821
410 Tucker Hall

http://www.biosci.missouri.edu/setzer/setzlab-mu.htm

Research description

We are interested in the control of transcription of eukaryotic genes, and in particular the basic molecular mechanisms governing the interaction of transcription regulatory factors with each other and with specific DNA sequences. Specific projects include: (1) analysis of 5S rRNA gene transcription by RNA polymerase III, (2) understanding specific DNA (and RNA) sequence recognition by zinc finger proteins, particularly the archetypal zinc finger protein TFIIIA, (3) applying novel approaches to the study of the mechanism of transcriptional activation, and (4) defining the mechanism of transcription termination using a unique kinetic approach. The model systems we study include the frog Xenopus laevis and the yeasts Saccharomyces cerevisiae (budding yeast) and Schizosaccharomyes pombe (fission yeast). We also make use of cultured eukaryotic cell lines.

Our experimental approaches include rigorous, quantitative analyses of in vitro transcription reactions and of the interactions of transcription factors with each other and with their DNA targets. This in vitro biochemical approach is complemented by genetic analyses in yeast and, at times, by experiments making use of microinjection into and manipulation of Xenopus eggs and embryos. Our efforts are focused on understanding the fundamental molecular mechanisms governing gene expression, but have sometimes been known to have practical consequences. For example, our recent studies of certain mutant forms of TFIIIA are relevant to the engineering of novel proteins that make use of the zinc finger motif to recognize specific DNA sequences in gene therapy or gene targeting approaches.

Selected publications

Schmidt, F.J. and Setzer, D.R. 2010. RNA: Transcription and RNA processing. In Biochemistry, 7th ed., T.M. Devlin, Editor. Wiley-Liss.

Gunther, C., Corey, D.A., and Setzer, D.R. 2009. Determinants of structural stability and function in a single zinc finger: analysis of alanine-substitution mutations in zinc finger 8 of Xenopus laevis TFIIIA. In preparation.

Setzer, D.R., Schulman, D.B., Gunther, C.V., and Bumbulis, M.J. 2009. Use of a reporter gene assay in yeast for genetic analysis of DNA-protein interactions. Methods Mol. Biol. 543, 219-241.

Brady, K.L. and Setzer, D.R. 2005. Is there a dynamic DNA-protein interface in the TFIIIA-5S rRNA gene complex? J. Biol. Chem. 280, 16115-16124.

Brady, K.L., Ponnampalam, S.N., Bumbulis, M.J., and Setzer, D.R. 2005. Mutations in TFIIIA that increase stability of the TFIIIA-5S rRNA gene complex: unusual effects on the kinetics of complex assembly and dissociation. J. Biol. Chem. 280, 26743-26750.

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