Molecular Pharmacology, Vol 16, 297-305, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Polyribonucleotide Inhibition of Ribonucleic Acid Directed Deoxyribonucleic Acid Polymerase of Mouse Mammary Tumor (Type B) Virus and Simian Sarcoma (Type C) Virus

¹ Viral Oncology and Molecular Pathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

The response of the RNA-directed DNA polymerases of mouse mammary tumor virus (MMTV) and simian sarcoma virus (SiSV) to synthetic polynucleotides is investigated in this study. Detergent-disrupted, virus-associated—as well as partially purified DNA polymerase—activities were analyzed. DNA polymerase activities from both viruses were inhibited by single-stranded polyribonucleotides. While no major qualitative differences were found, the quantitative responses of the DNA polymerases of the two viruses were different. Analysis of inihibition kinetics revealed the following order of inhibitory potency: Poly(U) > poly(I) » poly(A) for MMTV DNA polymerase and poly(I) > poly(U) » poly(A) for SiSV DNA polymerase. Poly(A) was less and poly(U) was more inhibitory for SiSV DNA polymerase when compared with MMTV DNA polymerase. In addition, MMTV DNA polymerase displayed roughly the same affinity for the template: primers poly(A):oligo(dT) and poly(C):oligo(dG). In contrast, SiSV DNA polymerase preferred poly(C):oligo(dG) over poly(A):oligo(dT).

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ACKNOWLEDGMENTS We thank Drs. Jack Gruber and Charles Benton for providing the preparations of mouse mammary tumor virus and simian sarcoma virus. We thank Dr. Cephas Patch for his assistance with computations. S.K.A. is an IPA research scientist at the National Cancer Institute, on leave of absence from Roswell Park Memorial Institute, Buffalo, New York.