The murine p53 protein blocks replication of SV40 DNA in vitro by inhibiting the initiation functions of SV40 large T antigen.
We have characterized the effect of murine p53 on SV40 DNA replication in vitro. Purified wild-type murine p53 dramatically inhibited the ability of SV40 T antigen to mediate the replication of a plasmid bearing the viral origin (ori-DNA) in vitro. In contrast, polyoma ori-DNA replication in vitro was unaffected by p53. Surprisingly, both unbound p53 and SV40 T antigen-bound p53 were equally detrimental to SV40 ori-DNA replication. Thus, p53 interferes with interactions between T antigen molecules that are required for DNA synthesis. p53 inhibited the binding to and subsequent unwinding of the SV40 origin by T antigen and thus selectively blocked the initial stages of ori-DNA replication. In contrast to the nononcogenic wild-type murine p53, high concentrations of a mutant transforming p53 failed to block SV40 ori-DNA replication in vitro. These observations may provide insight into a possible role for p53 in the cell.
Wang
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EH
Department of Biological Sciences, Columbia University, New York, New York 10027.
Friedman
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PN
Prives
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C
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000235:genetics*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism / Q000494:pharmacology*; D010957:Plasmids; D013539:Simian virus 40 / Q000235:genetics*; D014170:Transformation, Genetic; D016159:Tumor Suppressor Protein p53
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53