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.
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