1887

Abstract

SUMMARY

A homology search of proteins predicted from the recently reported complete DNA sequence of varicella-zoster virus (VZV) revealed that the product of gene 13 was highly homologous to eukaryotic and prokaryotic thymidylate synthetases (TSs). The VZV protein was shown to be a TS by three functional tests. Firstly, a plasmid designed to express the native protein was able to complement a strain of in which the natural TS gene is deleted. Secondly, in an enzyme assay for TS, extracts of the complemented strain were capable of releasing tritiated water from 2′-deoxy[5- H]uridylate. Thirdly, these extracts contained a protein that bound isotopically labelled 5-fluoro-2′-deoxyuridylate, a ligand specific for the active site of TS. In addition, a novel ligand-binding protein was detected in human cells infected with VZV.

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1987-05-01
2021-10-18
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References

  1. Amann E., Brosius J. 1985; ‘ATG vectors’ for regulated high-level expression of cloned genes in Escherichia coli . Gene 40:183–190
    [Google Scholar]
  2. Ayusawa D., Iwata K., Seno T., Koyama H. 1981; Conditional thymidine auxotrophic mutants of mouse FM3A cells due to thermosensitive thymidylate synthase and their prototrophic revertants. Journal of Biological Chemistry 256:12005–12012
    [Google Scholar]
  3. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. c., Seguin C., Tuffnell P. s., Barrell B. G. 1984; DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature; London: 310207–211
    [Google Scholar]
  4. Belfort M., Maley G., Pedersen-Lane J., Maley F. 1983; Primary structure of the Escherichia coli thyA gene and its thymidylate synthase product. Proceedings of the National Academy of Sciences, U.S.A 80:4914–4918
    [Google Scholar]
  5. Belfort M., Pedersen-Lane J., West D., Ehrenman K., Maley G., Chu F., Maley F. 1985; Processing of the intron-containing thymidylate synthase (td) gene of phage T4 is at the RNA level. Cell 41:375–382
    [Google Scholar]
  6. Beverley S. M., Ellenberger T. E., Cordingley J. S. 1986; Primary structure of the gene encoding the bifunctional dihydrofolate reductase-thymidylate synthase of Leishmania major . Proceedings of the National Academy of Sciences, U.S.A 83:2584–2588
    [Google Scholar]
  7. Chu F. K., Maley G. F., Maley F., Belfort M. 1984; An intervening sequence in the thymidylate synthase gene of bacteriophage T4. Proceedings of the National Academy of Sciences, U.S.A 81:3049–3053
    [Google Scholar]
  8. Chu F. K., Maley G. F., Belfort M., Maley F. 1985; In vitro expression of the intron-containing gene for T4 phage thymidylate synthase. Journal of Biological Chemistry 260:10680–10688
    [Google Scholar]
  9. Davison A. J., Scott J. E. 1986; The complete DNA sequence of varicella-zoster virus. Journal of General Virology 67:1759–1816
    [Google Scholar]
  10. Davison A. J., Wilkie N. M. 1983; Location and orientation of homologous sequences in the genomes of five herpesviruses. Journal of General Virology 64:1927–1942
    [Google Scholar]
  11. Davison A. J., Waters D. J., Edson C. M. 1985; Identification of the products of a varicella-zoster virus glycoprotein gene. Journal of General Virology 66:2237–2242
    [Google Scholar]
  12. Doberson M. J., Jerkofsky M., Greer S. 1976; Enzymatic basis for the selective inhibition of varicella-zoster virus by 5-halogenated analogs of deoxycytidine. Journal of Virology 20:478–486
    [Google Scholar]
  13. Dowbenko D. j., Lasky L. A. 1984; Extensive homology between the herpes simplex virus type 2 glycoprotein F gene and the herpes simplex virus type 1 glycoprotein C gene. Journal of Virology 52:154–163
    [Google Scholar]
  14. Draper K. G., Frink R. J., Devi G. B., Swain M., Galloway D., Wagner E. K. 1984; Herpes simplex virus types 1 and 2 homology in the region between 0·58 and 0·68 map units. Journal of Virology 52:615–623
    [Google Scholar]
  15. Dubbs D. R., Kitt S. 1974; Mutant strains of herpes simplex deficient in thymidine kinase-inducing activity. Virology 22:493–502
    [Google Scholar]
  16. Dumas A. M., Geelen J. L. M. C., Weststrate M. W., Wertheim P., Van Der Noordaa J. 1981; XbaI, PstI and BglII restriction endonuclease maps of the two orientations of the varicella-zoster virus genome. Journal of Virology 39:390–400
    [Google Scholar]
  17. Ellis R. w., Keller P. M., Lowe R. s., Zivin R. A. 1985; Use of a bacterial expression vector to map the varicella-zoster virus major glycoprotein gene, gC. Journal of Virology 53:81–88
    [Google Scholar]
  18. Frink R. J., Eisenberg R., Cohen G., Wagner E. K. 1983; Detailed analysis of the portion of the herpes simplex virus type 1 genome encoding glycoprotein C. Journal of Virology 45:634–647
    [Google Scholar]
  19. Grumont R., Washtien W. L., Caput D., Santi D. V. 1986; Bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica: sequence homology with the corresponding monofunctional proteins. Proceedings of the National Academy of Sciences, U.S.A 83:5387–5391
    [Google Scholar]
  20. Honess R. W., O’Hare P., Young D. 1982; Comparison of thymidine kinase activities induced in cells productively infected with herpesvirus saimiri and herpes simplex virus. Journal of General Virology 58:237–249
    [Google Scholar]
  21. Honess R. W., Bodemer W., Cameron K. R., Niller H.-H., Fleckenstein B., Randall R. E. 1986; The A+T- rich genome of herpesvirus saimiri contains a highly conserved gene for thymidylate synthase. Proceedings of the National Academy of Sciences, U.S.A 83:3604–3608
    [Google Scholar]
  22. Jenh C.-H., Geyer P. K., Baskin F., Johnson L. F. 1985; Thymidylate synthase gene amplification in fluorodeoxyuridine-resistant mouse cell lines. Molecular Pharmacology 28:80–85
    [Google Scholar]
  23. Keller P. M., Davison A. J., Lowe R. S., Bennett C. D., Ellis R. W. 1986; Identification and structure of the gene encoding gpII, a major glycoprotein of varicella-zoster virus. Virology 152:181–191
    [Google Scholar]
  24. Keller P. M., Davison A. J., Lowe R. S., Reimen M., Ellis R. w. 1987; Identification and sequence of the gene encoding gpIII, a major glycoprotein of varicella-zoster virus. Virology in press
    [Google Scholar]
  25. Kenny E., Atkinson T., Hartley B. S. 1985; Nucleotide sequence of the thymidylate synthetase gene (thyPi) from Bacillus subtilis phage 𝜙3T. Gene 34:335–342
    [Google Scholar]
  26. Lockshin A., Moran R. G., Danenberg P. V. 1979; Thymidylate synthase purified to homogeneity from human leukemic cells. Proceedings of the National Academy of Sciences, U.S.A 76:750–754
    [Google Scholar]
  27. Mcgeoch D. J., Davison A. J. 1986; Alphaherpesviruses possess a gene homologous to the protein kinase gene family of eukaryotes and retroviruses. Nucleic Acids Research 14:1765–1777
    [Google Scholar]
  28. Maley G. F., Bellisario R. L., Guarino D. U., Maley F. 1979; The primary structure of Lactobacillus casei thymidylate synthetase. Journal of Biological Chemistry 254:1301–1304
    [Google Scholar]
  29. Maley G. F., Maley F., Baugh C. M. 1982; Studies on identifying the folylpolyglutamate binding sites of Lactobacillus casei thymidylate synthetase. Archives of Biochemistry and Biophysics 216:551–558
    [Google Scholar]
  30. Roberts D. 1966; An isotopic assay for thymidylate synthetase. Biochemistry 5:3546–3548
    [Google Scholar]
  31. Shiraki K., Ogino T., Yamanishi K., Takahashi M. 1983; Isolation of drug resistant mutants of varicella-zoster virus: cross resistance of acyclovir resistant mutants with phosphonoacetic acid and bromodeoxyuridine. Biken Journal 26:17–23
    [Google Scholar]
  32. Takeishi K., Kaneda S., Ayusawa D., Shimizu K., Gotoh O., Seno T. 1985; Nucleotide sequence of a functional cDNA for human thymidylate synthase. Nucleic Acids Research 13:2035–2043
    [Google Scholar]
  33. Wagner E. K. 1985; Individual HSV transcripts. Characterization of specific genes. In The Herpesviruses 3 pp. 45–104 Roizman B. Edited by New York: Plenum Press;
    [Google Scholar]
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