The temperate phase P1 is unusual because its prophage is a plasmid. The studies proposed are genetic and biochemical approaches to learning more about the regulatory mechanisms that determine when viral genes are expressed and which mode of DNA replication (plasmid or viral) is employed. Specifically, studies involving expression of superinfection immunity and prophage repression are planned. Because of its extrachromosomal form, prophage P1 serves as a model both for antibiotic resistance plasmids and for animal viruses like the carcinogenic Epstein-Barr virus (EBV). The plasmid DNA form of EBV is found in Burkitt lymphoma cells and in the Raji cell line, and thus appears to be involved in transformation. We hope that a better understanding of the mechanisms in P1 that control maintenance of the prophages will help in understanding the maintenance of the plasmid form of EBV and other similar animal viruses. In addition, a site-specific recombination system in P1 appears to be involved in regulation of gene expression. Since oncornaviruses integrate into cellular DNA during transformation by recombination at a specific site on an apparently closed covalent circular viral DNA copy, it is anticipated than an understanding of this phenomenon in bacteriophage P1 may be useful for understanding the importance of site-specific recombination in such viruses.
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