R. Graham Smith

Viral and Cellular DNA Polymerase: Comparison of Activities with Synthetic and Natural RNA Templates

Two DNA polymerases purified from normal human lymphocytes are distinguishable from the viral reverse transcriptases of avian myeloblastosis virus and Mason-Pfizer monkey virus by their relative affinity for select templates. In this respect, the activity of the two normal human lymphocyte polymerases closely resembles the activity of Escherichia coli DNA polymerase 1. The viral and cellular DNA polymerases are equally active with the nonspecific template, poly(rA) � poly(dT). Criteria for distinguishing the activity of viral reverse transcriptase are discussed.

Human DNA Polymerase III (R-DNA Polymerase): Distinction from DNA Polymerase I and Reverse Transcriptase

DNA polymerase III is an enzyme activity in eukaryotic cells which under certain conditions shows strong preference for polyadenylic acid as template when primed by oligodeoxythymidylate. Its first complete separation from other DNA polymerases in human lymphoblasts is reported. This enzyme is biochemically and immunologically distinct from DNA polymerase I and from viral reverse transcriptase from a primtate type C virus.

Reverse Transcriptase in Normal Rhesus Monkey Placenta

Particles with the morphology of type C virus have been identified from primate placentas by electron microscopy. A reverse transcriptase (RNA-dependent DNA polymerase) was isolated and purified from microsomal pellets of two fresh placentas of rhesus monkeys in the early stages of gestation. This enzyme was biochemically similar yet immunologically distinct from the reverse transcriptases of known tumorigenic type C RNA viruses isolated from primates, but was immunologically related to a reverse transcriptase isolated from a type C virus obtained from normal baboon placenta. These particles may represent endogenous viruses and may function in the transfer of genetic information during embryogenesis.

DNA polymerases from RNA tumor viruses and human cells: inhibition by polyuridylic acid.

Polyuridylic acid inhibited DNA polymerases purified from three species of oncornaviruses as well as three out of seven DNA polymerases purified from cells. Viral and cellular DNA polymerases could not be distinguished by polyuridylic acid inhibition, but were easily distinguished by their template preferences in the presence of magnesium.

Agents which inhibit reverse transcriptases

Abstract In this brief review, we will begin by outlining a plausible rationale for the development of inhibitors of the DNA polymerases of RNA tumor viruses (reverse transciptases). Then, rather than exhaustively describing all agents which have been shown to inhibit these enzymes, we will present a classification of these inhibitors based on the biochemical properties of the enzymes and the mechanism of action of the inhibitors, offer a critique of existing inhibitors, and suggest directions for future research.