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curriculum vitae

The Duina Laboratory

Research Interests

The first step in utilizing genetic information for protein synthesis is the production of RNA molecules. The process of making RNA from DNA, referred to as transcription, has been the subject of intense research over the past several decades. In my laboratory, we are particularly interested in the proteins that package DNA to create chromosomes, as well as the proteins that modify this packaging to ensure proper gene transcription. For our studies, we use the budding yeast Saccharomyces cerevisiae as a model system. Yeast is an excellent experimental organism for several reasons, including the fact that it is highly amenable to a variety of genetic and molecular approaches. Given the remarkable evolutionary conservation between the basic molecular mechanisms that occur in yeast and in human cells, our research is also likely to further our knowledge of basic aspects of human cell biology.

Our previous studies have focused on the nucleosome, the basic repeating unit of chromosomes. The nucleosome is a disc-like structure composed of a short stretch of DNA wrapped around two sets of four proteins known as histones. Our experiments have identified a novel mutation in one of the histones, histone H3, that impairs normal transcriptional control. This mutant H3, hht2-11, encodes a single amino acid substitution at position 61, converting a leucine into a tryptophan (H3-L61W). Using a combination of different experimental approaches, we have demonstrated that this mutation affects the ability of chromosomes to interact with Swi/Snf, a conserved protein complex that controls transcription by modulating chromosome structure. Furthermore, we have isolated and analyzed additional mutations that suppress hht2-11. These include new alleles of the SPT16 gene, which encodes an essential and highly conserved protein factor that is involved in transcriptional elongation. Like Swi/Snf, wild-type Spt16 interacts with nucleosomes, and this association is impaired by the H3-L61W mutation.

(The above figure of the nucleosome is taken from Duina and Winston, 2004 and kindly provided by Cindy L. White and Karolin Luger.)

These results support the view that chromosome structure can have profound effects on transcription, a picture that has also emerged from the work of many in the field. Furthermore, these findings indicate that our experimental strategy provides a powerful and productive system. As such, current research projects in my laboratory are using this approach to gain further insight into the dynamic relationship between chromosomes and transcription.

Publications

• Duina, A.A. and F. Winston. 2004. Analysis of a histone H3 mutant that perturbs association of Swi/Snf with chromatin. Mol. Cell. Biol. 24, 561- 72.
• Duina, A.A., H.M. Kalton, and R.F. Gaber. 1998. Requirement for Hsp90 and a CyP-40-type cyclophilin in negative regulation of the heat shock response. J. Biol. Chem. 273,18974-18978.
• Duina, A.A., J.A. Marsh, R.B. Kurtz, J.H.-C. Chang, S. Lindquist, and R.F. Gaber. 1998. The peptidyl-prolyl isomerase domain of the CyP-40 cyclophilin homolog Cpr7 is not required to support growth or glucocorticoid receptor activity in Saccharomyces cerevisiae. J. Biol. Chem. 273, 10819-10822.
• Duina, A.A., J.H.-C. Chang, J.A. Marsh, S. Lindquist, and R.F. Gaber. 1996. A cyclophilin function in Hsp90- dependent signal transduction. Science 274, 1713-1715.
• Duina, A.A., J.A. Marsh, and R.F. Gaber. 1996. Identification of two CyP-40-like cyclophilins in Saccharomyces cerevisiae, one of which is required for normal growth. Yeast 12, 943-952.

Members of the Lab

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