SUMMARYInhibitors of bacterial DNA gyrase and eukaryotic DNA topoisomerase (novobiocin and nalidixic acid) were investigated with respect to their effect on the activity of RNA-dependent DNA polymerases from murine and avian retroviruses. Purified RNA-dependent DNA polymerase from AKR virus was inhibited more than 90~ by 0-3 mg/ml and almost completely by 1 mg/ml of the drugs when poly(A)-oligo(dT)l 2-1 s was used as a template-primer. In contrast to the enzyme from AKR virus, purified enzyme from avian myeloblastosis virus was less sensitive, i.e. nearly 50~ activity remained even in the presence of I mg/ml of the drugs with the same template-primer. RNA-dependent DNA polymerase activity in AKR virus particles was inhibited, but was resistant to low concentrations of the drugs. The inhibition was not due to specific interaction between drugs and the template-primer or labelled precursor, since RNAdependent DNA polymerase was inhibited by the drugs with activated calf thymus DNA or poly(C), oligo(dG)l 2-1 s as the template. Endogenous DNA synthesis by AKR virus particles was inhibited by novobiocin to the same extent.RNA-dependent DNA polymerase (RDDPase) plays a central role during the life cycle of retroviruses. After retrovirus infection of cells, it uses viral RNA as a template for singlestranded DNA and the single-stranded DNA is then converted to linear double-stranded DNA (Verma, 1977(Verma, , 1981. The linear double-stranded DNA molecules are further converted into covalently closed circular DNA which is subsequently integrated into the host chromosomal DNA. Although the precise mechanism remains unknown, RDDPase may play an important role in the above reaction with the possible cooperation of host-derived factors (HaginoYamagishi et al., 1981).
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