DNA Polymerases from RNA Tumor Viruses and Human Cells: Inhibition by Polyuridylic Acid

Abstract

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.

Inhibition of oncornavirus functions by 2'-azido polynucleotides.

“…However, poly(U) and its 2'-fluorinated analogue poly(dUfl) were not active templates for the DNA polymerase of avian myeloblastosis virus when primed with (dA)lo (5,22). In the absence of a primer, poly(U) inhibited the polymerization reaction (1)(2)(3)(4)(5), and this inhibition was augmented upon introduction of a chlorine or fluorine substituent in the 2'-OH position of poly(U) (5). Poly(C), which can hardly be considered as an inhibitor of oncornavirus DNA polymerase (1,5), became markedly effective after substitution of 2'-OH by 2'-Cl (5).…”

“…have been reported to inhibit the DNA polymerase activity of a number of oncornaviruses [Rauscher murine leukemia virus (MuLV), Moloney murine leukemia virus, avian myeloblastosis virus, etc.] (1)(2)(3)(4)(5)(6). This inhibitory effect was ascribed to a competitive binding of the synthetic homopolyribonucleotide with the template site of the polymerase (1,5,6).…”

“…This inhibitory effect was ascribed to a competitive binding of the synthetic homopolyribonucleotide with the template site of the polymerase (1,5,6). Poly(U) exhibited some selectivity in that the polymer inhibited the DNA polymerase activity of Rauscher murine leukemia virus but not that-of mouse embryo or Escherichia coli (1), but the hope that poly(U) might be a useful tool for distinguishing DNA polymerase of oncornaviruses from cellular DNA polymerases (1) did not appear justified (2).…”

Lysine-329 of murine leukemia virus reverse transcriptase: possible involvement in the template-primer binding function

“…These results appear to suggest that OAPA-reactive site(s) may be important in recognition and binding of polynucleotide templates. The affinity and binding of polynucleotides to RTs has been well documented (Abrell et al, 1972;Srivastava, 1973;Marcus et al, 1974;Erickson, 1975). The loss of template-primer binding ability of OAPA-treated enzyme (Figure 2) is consistent with the implication of an OAPAreactive site in binding function.…”