The experiments in this proposal concern the fate of the genome of polyoma virus in infections of nonpremissive rat cells (Fischer rat F-111). The major question consists of an elucidation of the steps involved in the integration pathway of the viral genome into the host genome. concomitant with stable neoplastic transformation of these cells. Many questions center around the role of interviral recombination and viral DNA replication and the role of the viral large T-antigen in any aspect of the process. There are four major section. The first concerns studies of factors which affect the process. For example we are asking whether the events related to integration occur in specific phases of the cell cycle. The second concerns the role of large T- antigen. For example we are asking whether increasing the amounts of large T-antigen in all cells from the beginning of infection will alter the events correlated with integration. The third section is a study of integrated viral structures. We will make comsid libraries to study whether the viral genome integrate in specific regions of the host chromatin (e.g. DNAse sensitive sites) and whether integration events in a single transformants are independent. The fourth section consists of studies of competition for integration between viral genomes of different parental origin.
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