An understanding of retroviral mechanisms is of interest to the medical community and the general public, because of the role of viruses in infections (such a HIV and other T-cell viruses) and cancer that result from transfer and misregulation of proto-oncogenes. The proposed project is to identify yeast genes involved in the transposition cycle of the yeast retroelement Ty1. The Ty1 element transposes via a mechanism bearing many similarities to retroviruses which infect larger eukaryotes. Ty1 is a good model system, as dissection of the Ty1 transposition pathway is facilitated by the ease of yeast molecular genetic techniques. Transposition of Ty1 is known to be temperature sensitive. The immediate goals of this project are to determine the effects of temperature on the transposition process, and to clone mutant yeast genes which allow transposition to occur at elevated temperatures. The long-term goal for the project will be to determine the function of these cloned host genes in the transposition process. Comparative biochemical studies of Ty1 virus-like particles (VLPs) isolated from mutant and wild-type strains will enable the determination of their role in transposition. If the cloned genes have not been previously studied, genetic studies will be initiated to determine the cellular function of the genes. Long-term objectives beyond this proposal period will be to identify the counter- parts of the cloned genes in larger eukaryotes. This will give clues as to how viruses utilize host genes and may eventually allow for strategic interference of viral life-cycles.
| Radford, Sarah J; Boyle, Meredith L; Sheely, Catherine J et al. (2004) Increase in Ty1 cDNA recombination in yeast sir4 mutant strains at high temperature. Genetics 168:89-101 |
| Lawler Jr, Joseph F; Haeusser, Daniel P; Dull, Angie et al. (2002) Ty1 defect in proteolysis at high temperature. J Virol 76:4233-40 |
