Section on Eukaryotic Transposable Elements

Head: Henry L. Levin

Diseases caused by retroviruses such as AIDS and leukemia have intensified the need to understand the mechanisms of retrovirus replication. Our primary objective is to understand how retroviral cDNAs are integrated into the genome of infected cells. Because of their similarities to retroviruses, long terminal repeat (LTR) retrotransposons are important models for retrovirus replication. The retrotransposon under study in our laboratory is the Tf1 element of the fission yeast Schizosaccharomyces pombe. One principal goal is to determine how the integrase enzyme disrupts host DNA and simultaneously introduces full-length copies of viral cDNA. We are particularly interested in the strong preferences of human immunodeficiency virus 1 (HIV-1) and murine leukemia virus (MLV) for integration into pol II transcription units. Little is known about how these viruses recognize their target sites. With its strong preference for integrating into pol II promoters and its similarity to HIV-1, Tf1serves as a model system. An understanding of the mechanisms responsible for targeted integration may lead to new approaches for blocking the replication of HIV-1.

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