Autonomous parvovirus DNA replication requires topoisomerase I and its activity is increased during infection.
Topoisomerases I and II (topo I and topo II) are nuclear enzymes functioning to resolve DNA topological problems during replication, transcription, and other DNA processes. We tested the effects of camptothecin and VP16, specific inhibitors of topo I and II, respectively, on the DNA replication of parvoviruses LuIII and H-1 and found that viral DNA synthesis was suppressed by camptothecin but not by VP16. Transcription of H-1 virus was measured by a nuclear runoff assay and showed no inhibition by camptothecin. Interestingly, topo I in the LuIII virus-infected cell nuclear extract appears to have more activity for covalently binding to viral DNA than that in mock-infected cell nuclear extracts. Our data suggested that this activity was not due to an increased transcription of the topo I gene or to greater amounts of topo I.
Gu
M L
ML
Eppley Institute, University of Nebraska Medical Center, Omaha 68105-1065.
Rhode
S L
SL
D002166:Camptothecin / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002472:Cell Transformation, Viral; D004261:DNA Replication / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D010321:Parvoviridae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D004264:DNA Topoisomerases, Type I; D002166:Camptothecin