David A. Brow
 |
Professor
Office: (608) 262-1475 |
Education
- BA 1979, University of California, Santa Cruz;
- PhD 1986, University of California, San Diego;
- Postdoctoral, 1986-89, University of California, San Francisco (C. Guthrie).
Honors & Awards
- Searle Scholar Award, 1990;
- Shaw Scientist Award, 1991.
Research Interests
We investigate the molecular mechanisms of eukaryotic gene expression, with emphasis on transcription and pre-mRNA splicing. Because the fundamental mechanisms of gene expression are conserved among eukaryotes, we have chosen the genetically tractable yeast S. cerevisiae as a model system. Our transcription studies focus on how RNA polymerases (Pol) II and III identify a gene, and on the detailed mechanism of initiation and termination of transcription by Pol II. We use genetic, genomic, and biochemical approaches in these studies. For example, we have measured Pol II occupancy across the entire yeast genome at 100-200 base-pair resolution by chromatin immunoprecipitation, and we have identified mutations in Pol II that cause it to “read-through” transcription terminators. We discovered and are characterizing a Pol II termination pathway that uses the helicase Sen1 and appears to be most important for short transcripts. In our splicing studies we examine the mechanism and function of dynamic RNA-RNA and RNA-protein interactions in assembling the active site of the spliceosome. We defined a complex network of genetic interactions that involve two RNAs (U4 and U6), two helicases, an RNA-binding protein, and the largest and most conserved spliceosomal protein (Prp8). We use detailed mutational studies, in vitro splicing and RNA-binding assays, and structural biology to dissect the mechanism of spliceosome activation. Mutations in the human Prp8 and Sen1 genes cause retinal degeneration and progressive motor neuron dysfunction, respectively. We hope our studies will illuminate the mechanisms of these diseases.
Publications of Note
Kuehner, J.N, and D.A. Brow. (2006). Quantitative analysis of in vivo initiator selection by yeast RNA polymerase II supports a scanning model. J. Biol. Chem. 281, 14119-14128.
Steinmetz, E.J., S.B.H. Ng, J.P. Cloute, and D.A. Brow. (2006). Cis- and trans-acting determinants of transcription termination by yeast RNA polymerase II. Molec. Cell. Biol. 26, 2688-2696.
Butcher, S. and Brow, D.A. (2005). Towards understanding the catalytic core structure of the spliceosome. Biochem. Soc. Transact. 33, 447-449.
Kwan, S.S. and D.A. Brow. (2005). The N- and C-terminal RNA recognition motifs of splicing factor Prp24 have distinct functions in U6 RNA binding. RNA 11, 808-820.
Kaiser, M.W., J. Chi and D.A. Brow. (2004). Position-dependent function of a B block promoter element implies a specialized chromatin structure on the S. cerevisiae U6 RNA gene, SNR6. Nucl. Acids Res. 32, 4297-4305.
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University
of Wisconsin - Department
of Biomolecular Chemistry
First published: 01/01/05 Last updated:
7/11/06 Email Biomolecular Chemistry
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