REPLICON CONTROL IN NORMAL AND TRANSFORMING CELLS

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The interaction of parvovirus with its host cell is being used as a probe of eukaryotic cell differentiation, DNA replication, and aging. We will explore the properties of parvovirus early and late promoters and the interaction between them. The early promoter produces a gene product that positively regulates the late promoter. The mechanisms and sequences involved in this trans-activation will be studied. The parvovirus early promoter will be tested for dependence on a host cell regulatory protein and cell lines suitable for cloning the gene for such a protein isolated. In the terminal stages of fibroblast differentiation, the senescing cells become resistant to parvovirus infection and these cells will be tested for restriction of virus early promoter activity.