Jef D. Boeke
Transposition Mechanisms; Reverse Transcription in Genome Evolution; Yeast Molecular Genetics; Antiviral Strategies
We study the yeast retrovirus-like transposable element, Ty1. This element is a "retrotransposon" that moves from one site in the DNA to another, via a reverse transcriptase-mediated process in which a full-length Ty1 RNA molecule is converted to DNA by Ty1 reverse transcriptase. This is followed by integration into host DNA. Many of these events take place in an intracellular virus-like particle, the transposition intermediate. We study the mechanism of retrotransposition, with a special focus on host factors that are used in reverse transcription and integration - proteins associated with RNA processing and the cell cycle appear to be involved in Ty1 transposition. These genetic studies are complemented by experiments in cell-free reverse transcription and integration systems. Studies of retrotransposons in man are also underway. Finally, we have developed a novel antiviral strategy in which viral coat proteins are fused to destructive nucleases; the nucleases are targeted to virus particles during the assembly process, and eventually kill the virus. We are applying this strategy to retroviruses.