1887

Abstract

SUMMARY

Mammalian ribonucleotide reductase is a complex enzyme modified in its activity by a complex regulatory system involving adenosine triphosphate (ATP) and deoxyribonucleoside triphosphates. Infection of KB cells with herpes simplex virus (HSV) type 1 or 2 induces the formation of an altered ribonucleotide reductase. The properties of partially purified reductase from uninfected KB cells have been compared with the enzymes obtained from HSV-1 and HSV-2 infected KB cells. We found that the virus-induced enzymes are similar to the KB enzyme in some properties but differed significantly from the host enzyme in three respects: (1) virus induced reductase was not inhibited significantly by deoxythymidine triphosphate regardless of ATP concentration, (2) magnesium was not required for virus enzyme activity although 2 m-Mg did stimulate the reaction, and (3) magnesium concentration required for optimal activity was different for virus and host enzymes. These changes are evidence that the enzyme molecules present after infection by HSV-1 or HSV-2 differ from those present before infection.

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1977-07-01
2024-04-24
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References

  1. Berglund O. 1972a; Ribonucleoside diphosphate reductase induced by bacteriophage T4. I. Purification and characterization. The Journal of Biological Chemistry 247:7270–7275
    [Google Scholar]
  2. Berglund O. 1972b; Ribonucleoside diphosphate reductase induced by bacteriophage T4. II. Allosteric regulation of substrate specificity and catalytic activity. The Journal of Biological Chemistry 247:7276–7281
    [Google Scholar]
  3. Berglund O., Karlstrom O., Reichard P. 1969; A new ribonucleotide reductase activity after infection with phage T4. Proceedings of the National Academy of Sciences of the United States of America 62:829–835
    [Google Scholar]
  4. Bjursell G., Reichard P. 1973; Effects of thymidine on deoxyribonucleoside, triphosphate pools and deoxyribonucleic acid synthesis in Chinese hamster ovary cells. The Journal bf Biological Chemistry 238:3904–3909
    [Google Scholar]
  5. Brown N. C., Canellakis Z. N., Lundin B., Reichard P., Thelander L. 1969; Ribonucleoside diphoSphate reductase. Purification of the two subunits, proteins Bi and B2. EuropeanJournal of Biochemistry 9:561–573
    [Google Scholar]
  6. Camiener G. W. 1968; Studies of the enzymatic deamination of ara-cytidine-V. Inhibition in vitro and in vivo by tetrahydrouridine and other reduced pyrimidine nucleosides. Biochemical Pharmacology 17:1981–1991
    [Google Scholar]
  7. Cheng Y.-C., Goz B., Prusoff W. H. 1975; Deoxyribonucleotide metabolism in herpes simplex virus infected HeLa cells. Biochimica et Biophysica Acta 390:253–263
    [Google Scholar]
  8. Cohen G. H., Vaughan R. K., Lawrence W. C. 1971; Deoxyribonucleic acid synthesis in synchronized mammalian KB cells infected with herpes simplex virus. Journal of Virology 7:783–791
    [Google Scholar]
  9. Cohen G. H. 1972; Ribonucleotide reductase activity of synchronized KB cells infected with herpes simplex virus. Journal of Virology 9:408–418
    [Google Scholar]
  10. Cohen G. H., Factor M. N., Ponce De Leon M. 1974; Inhibition of herpes simplex virus type 2 replication by thymidine. Journal of Virology 14:20–25
    [Google Scholar]
  11. Cohen J. C., Perdue M. L., Randall C. C., O’callaghan D. J. 1975; Replication of equine herpes virus type 1: resistance to hydroxyurea. Virology 67:56–67
    [Google Scholar]
  12. Elford H. L. 1972; Functional regulation of mammalian ribonucleotide reductase. In Advances in Enzyme Regulation vol 10 Edited by George Weber. Elmsford, New York: Pergamon Press Inc;
    [Google Scholar]
  13. Fujioka S., Silber R. Purification and properties of ribonucleotide reductase from leukemic mouse spleen. The Journal of Biological Chemistry 245:1688–1693
    [Google Scholar]
  14. Hampar B., Derge J. G., Martos L. M., Tagmets M. A., Burroughs M. A. 1972; Sequence of spontaneous Epstein-Barr virus activation and selective DNA synthesis in activated cells in the presence of hydroxyurea. Proceedings of the National Academy of Sciences of the United States of America 69:2589–2593
    [Google Scholar]
  15. Hopper S. 1972; Ribonucleotide reductase of rabbit bone marrow. I. Purification properties into two protein fractions. The Journal of Biological Chemistry 247:3336–3340
    [Google Scholar]
  16. Jamieson A. T., Bjursell G. 1976a; Deoxyribonucleoside triphosphate pools in herpes simplex type I infected cells. Journal of General Virology 31:101–113
    [Google Scholar]
  17. Jamieson A. T., Bjursell O. 1976b; Deoxyribonucleoside triphosphate pools in cells infected with deoxy-pyrimidine kinaseless herpes simplex virus. Journal of General Virology 31:115–123
    [Google Scholar]
  18. Kaplan A. S. 1964; Studies on the replicating pool of viral DNA in cells infected with pseudorabies virus. Virology 24:19–25
    [Google Scholar]
  19. Keir H. M., Subak-Sharpe H., Shedden, W. H. I., Watson D. H., Wildy P. 1966; Immunological evidence for a specific DNA polymerase produced after infection by herpes simplex virus. Virology 30:154–157
    [Google Scholar]
  20. Klemperer H. G., Haynes G. R., Shedden W. I., Watson D. H. 1967; A virus-specific thymidine kinase in BHK-21 cells infected with herpes simplex virus. Virology 31:120–128
    [Google Scholar]
  21. Larsson A., Reichard P. 1966a; Enzymatic synthesis of deoxyribonucleotides. IX. Allosteric effects in the reduction of pyrimidine ribonucleotides by the ribonucleoside diphosphate reductase system of Escherichia coli. The Journal of Biological Chemistry 241:2533–2539
    [Google Scholar]
  22. Larsson A., Reichard P. 1966b; Enzymatic synthesis of deoxyribonucleotides. X. Reduction of purine ribonucleotides; allosteric behavior and substrate specificity of the enzyme system from Escherichia coli B. The Journal of Biological Chemistry 241:2540–2549
    [Google Scholar]
  23. Larsson A. 1969; Ribonucleotide reductase from regenerating rat liver. European Journal of Biochemistry 11:113–121
    [Google Scholar]
  24. Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. 1951; Protein measurement with the Folin phenol reagent. The Journal of Biological Chemistry 193:265–275
    [Google Scholar]
  25. Mele J., Glaser R., Nonoyama M., Zimmerman J., Rapp F. 1974; Observations on the resistance of Epstein-Barr virus DNA synthesis to hydroxyurea. Virology 62:102–111
    [Google Scholar]
  26. Moore E. C., Reichard P. 1964; Enzymatic synthesis of deoxyribonucleotides. VI. The cytidine diphosphate reductase system from Novikoff hepatoma. The Journal of Biological Chemistry 239:3453–3456
    [Google Scholar]
  27. Moore E. C., Hurlbert R. B. 1966; Regulation of mammalian deoxyribonucleotide biosynthesis by nucleotides as activators and inhibitors. The Journal of Biological Chemistry 241:4802–4809
    [Google Scholar]
  28. Randerath K., Randerath E. 1967; Thin-layer separation. Methods for nucleic acid derivatives. In Methods in Enzymology vol XII pp 323–347 Edited by Grossman L., Moldave K. New York: Academic Press;
    [Google Scholar]
  29. Reichard P. 1967; The biosynthesis of deoxyribose. In CIBA Lectures in Microbial Biochemistry pp 1–77 New York: John Wiley & Sons, Inc;
    [Google Scholar]
  30. Reichard P. 1972; Control of deoxyribonucleotide-synthesis in vivo and in vitro. In Advances in Enzyme Regulation vol 10 pp 3–16 Edited by George Weber. Elmsford, New York: Pergamon Press Inc;
    [Google Scholar]
  31. Roller B., Cohen G. H. 1976; Deoxyribonucleoside triphosphate pools in synchronized human cells infected with herpes simplex virus types I and 2. Journal of Virology 18:58–64
    [Google Scholar]
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