1887

Abstract

SUMMARY

By comparative sequence analysis of the herpes simplex virus type 1 DNA polymerase gene of strain Angelotti and a phosphonoacetic acid-resistant (PAA) derivative, the site of the PAA mutation was identified as a single nucleotide (C → T) conversion within the mapping limits of the known PAA mutations of strains KOS and 17. The conservative amino acid change at residue 719 from alanine to valine results in a radical change in the properties of the polymerase, rendering the mutant enzyme resistant to PAA and various antiviral compounds. Amino acid homologies as well as secondary structure analysis reveal that the PAA mutation is contained in a 14 amino acid sequence which is highly conserved, and detected in the central domain of prokaryotic and eukaryotic DNA polymerases.

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1987-05-01
2022-08-18
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References

  1. Aleström P., Akusjärvi G., Pettersson M., Pettersson U. 1982; DNA sequence analysis of the region encoding the terminal protein and the hypothetical N-gene product of adenovirus type 2. Journal of Biological Chemistry 257:13492–13498
    [Google Scholar]
  2. Argos P., Tucker A. D., Philipson L. 1986; Primary structural relationships may reflect similar DNA replication strategies. Virology 149:208–216
    [Google Scholar]
  3. Baer R., Bankier A. T., Biggin D. M., 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. Bolden A., Aucker S., Weissbach A. 1975; Synthesis of herpes simplex virus, vaccinia virus and adenovirus DNA in isolated HeLa cell nuclei. I. Effect of viral-specific antisera and phosphonoacetic acid. Journal of Virology 16:1584–1592
    [Google Scholar]
  5. Chalberg M. D., Englund P. T. 1979; Purification and properties of the deoxyribonucleic acid polymerase induced by vaccinia virus. Journal of Biological Chemistry 254:7812–7819
    [Google Scholar]
  6. Chartrand P., Stow N. D., Timbury M. C., Wilkie N. M. 1979; Physical mapping of paar mutations of herpes simplex virus type 1 and type 2 by intertypic marker rescue. Journal of Virology 31:265–276
    [Google Scholar]
  7. Coen D. M., Furman P. A., Gelep P. T., Shaffer P. A. 1982; Mutations in the herpes simplex virus DNA polymerase gene can confer resistance to 9-β-d-arabinofuranosyladenine. Journal of Virology 41:909–918
    [Google Scholar]
  8. Coen D. M., Aschman D. P., Gelep P. T., Retondo M. J., Weller S. K., Schaffer P. A. 1984; Fine mapping and molecular cloning of mutations in the herpes simplex virus DNA polymerase locus. Journal of Virology 49:236–247
    [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 M.-J., Preston V. G., Mcgeoch D. J. 1984; Determination of the sequence alteration in the DNA of the herpes simplex virus type 1 temperature-sensitive mutant tsK . Journal of General Virology 65:859–863
    [Google Scholar]
  11. Earl P. L., Jones E. V., Moss B. 1986; Homology between DNA polymerases of poxviruses, herpesviruses, and adenoviruses: nucleotide sequence of the vaccinia virus DNA polymerase gene. Proceedings of the National Academy of Sciences, U.S.A 83:3659–3663
    [Google Scholar]
  12. Field J., Gronostajski R. M., Hurwitz J. 1984; Properties of the adenovirus DNA polymerase. Journal of Biological Chemistry 259:9487–9495
    [Google Scholar]
  13. Frank K. B., Cheng Y.-C. 1985; Mutally exclusive inhibition of herpesvirus DNA polymerase by aphidicolin, phosphonoformate, and acyclic nucleoside triphosphate. Antimicrobial Agents and Chemotherapy 27:445–448
    [Google Scholar]
  14. Furman P. A., Coen D. M., St.Clair M. H., Schaffer P. A. 1981; Acyclovir-resistant mutants of herpes simplex virus type 1 express altered DNA polymerase or reduced acyclovir phosphorylating activities. Journal of Virology 40:936–941
    [Google Scholar]
  15. Garnier J., Osguthorpe D. J., Robson B. 1978; Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. Journal of Molecular Biology 120:97–120
    [Google Scholar]
  16. Gibbs J. S., Chiou H. c., Hall J. D., Mount D. w., Retondo M. J., Weller S. K., Coen D. M. 1985; Sequence and mapping analyses of the herpes simplex virus DNA polymerase gene predict a C-terminal substrate binding domain. Proceedings of the National Academy of Sciences, U.S.A 82:7969–7973
    [Google Scholar]
  17. Hall J. D., Furman P. A., St.Clair M. H., Knopf C. W. 1985; Reduced in vivo mutagenesis by mutant herpes simplex DNA polymerase involves improved nucleotide selection. Proceedings of the National Academy of Sciences, U.S.A 82:3889–3893
    [Google Scholar]
  18. Hopp T. p., Woods K. R. 1981; Prediction of protein antigenic determinants from amino acid sequences. Proceedings of the National Academy of Sciences, U.S.A 78:3824–3828
    [Google Scholar]
  19. Kallin B., Sternås L., Saemundssen A. K., Luka J., Jörnvall H., Eriksson B., Tao P.-Z., Nilsson M. T., Klein G. 1985; Purification of Epstein-Barr virus DNA polymerase from P3HR-1 cells. Journal of Virology 54:561–568
    [Google Scholar]
  20. Karplus P. A., Schulz G. E. 1985; Prediction of chain flexibility in proteins. A tool for the selection of peptide antigens. Naturwissenschaften 72:212–213
    [Google Scholar]
  21. Knopf C. W. 1986; Nucleotide sequence of the DNA polymerase gene of herpes simplex virus type 1 strain Angelotti. Nucleic Acids Research 14:8225–8226
    [Google Scholar]
  22. Knopf K.-W. 1979; Properties of herpes simplex virus DNA polymerase and characterization of its associated exonuclease activity. European Journal of Biochemistry 98:231–244
    [Google Scholar]
  23. Knopf K.-W., Kaufman E. R., Crumpacker C. S. 1981; Physical mapping of drug resistance mutations defines an active center of the herpes simplex virus DNA polymerase enzyme. Journal of Virology 39:746–757
    [Google Scholar]
  24. Kyte J., Doolittle R. F. 1982; A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology 157:105–132
    [Google Scholar]
  25. Laughon A., Scott M. P. 1984; Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins. Nature; London: 31025–30
    [Google Scholar]
  26. Liljas A., Rossman M. G. 1974; X-ray studies of protein interactions. Annual Review of Biochemistry 43:475–507
    [Google Scholar]
  27. Ollis D. L., Brick P., Hamlin R., Xuong N. G., Steitz T. A. 1985; Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP. Nature; London: 313762–766
    [Google Scholar]
  28. Quinn J. P., Mcgeoch D. J. 1985; DNA sequence of the region in the genome of herpes simplex virus type 1 containing the genes for DNA polymerase and the major DNA binding protein. Nucleic Acids Research 13:8143–8163
    [Google Scholar]
  29. Robson B., Suzuki E. 1976; Conformational properties of amino acid residues in globular proteins. Journal of Molecular Biology 107:327–356
    [Google Scholar]
  30. Smith T. F., Waterman M. S., Fitch W. M. 1981; Comparative biosequence metrics. Journal of Molecular Evolution 18:38–46
    [Google Scholar]
  31. Watabe K., Leusch M. S., Ito J. 1984; A 3′ to 5′ exonuclease is associated with phage 𝜙29 DNA polymerase. Biochemical and Biophysical Research Communications 123:1019–1026
    [Google Scholar]
  32. Yoshikawa H., Ito J. 1982; Nucleotide sequence of the major early region of bacteriophage 𝜙29. Gene 17:323–335
    [Google Scholar]
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