Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1987 Feb 11;15(3):1185–1198. doi: 10.1093/nar/15.3.1185

On the fidelity of DNA replication: herpes DNA polymerase and its associated exonuclease.

J Abbotts, Y Nishiyama, S Yoshida, L A Loeb
PMCID: PMC340517  PMID: 3029700

Abstract

Procaryotic DNA polymerases contain an associated 3'----5' exonuclease activity which provides a proofreading function and contributes substantially to replication fidelity. DNA polymerases of the eucaryotic herpes-type viruses contain similar associated exonuclease activities. We have investigated the fidelity of polymerases purified from wild type herpes simplex virus, as well as from mutator and antimutator strains. On synthetic templates, the herpes enzymes show greater relative exonuclease activities, and greater ability to excise a terminal mismatched base, than procaryotic DNA polymerases which proofread. On a phi X174 natural DNA template, the herpes enzymes are more accurate than purified eucaryotic DNA polymerases; the error rate is similar to E. coli polymerase I. However, conditions which abnegate proofreading by E. coli polymerase I have little effect on the herpes enzymes. We conclude that either these viral polymerases are accurate in the absence of proofreading, or the conditions examined have little effect on proofreading by the herpes DNA polymerases.

Full text

PDF
1185

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbotts J., Loeb L. A. DNA polymerase alpha and models for proofreading. Nucleic Acids Res. 1985 Jan 11;13(1):261–274. doi: 10.1093/nar/13.1.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abbotts J., Loeb L. A. On the fidelity of DNA replication. Lack of primer position effect on the fidelity of mammalian DNA polymerases. J Biol Chem. 1984 Jun 10;259(11):6712–6714. [PubMed] [Google Scholar]
  3. Abbotts J., Loeb L. A. On the fidelity of DNA replication: use of synthetic oligonucleotide-initiated reactions. Biochim Biophys Acta. 1985 Jan 29;824(1):58–65. doi: 10.1016/0167-4781(85)90029-6. [DOI] [PubMed] [Google Scholar]
  4. Battula N., Loeb L. A. The infidelity of avian myeloblastosis virus deoxyribonucleic acid polymerase in polynucleotide replication. J Biol Chem. 1974 Jul 10;249(13):4086–4093. [PubMed] [Google Scholar]
  5. Brutlag D., Kornberg A. Enzymatic synthesis of deoxyribonucleic acid. 36. A proofreading function for the 3' leads to 5' exonuclease activity in deoxyribonucleic acid polymerases. J Biol Chem. 1972 Jan 10;247(1):241–248. [PubMed] [Google Scholar]
  6. Byrnes J. J., Downey K. M., Que B. G., Lee M. Y., Black V. L., So A. G. Selective inhibition of the 3' to 5' exonuclease activity associated with DNA polymerases: a mechanism of mutagenesis. Biochemistry. 1977 Aug 23;16(17):3740–3746. doi: 10.1021/bi00636a002. [DOI] [PubMed] [Google Scholar]
  7. Chen Y. C., Bohn E. W., Planck S. R., Wilson S. H. Mouse DNA polymerase alpha. Subunit structure and identification of a species with associated exonuclease. J Biol Chem. 1979 Nov 25;254(22):11678–11687. [PubMed] [Google Scholar]
  8. Crute J. J., Wahl A. F., Bambara R. A. Purification and characterization of two new high molecular weight forms of DNA polymerase delta. Biochemistry. 1986 Jan 14;25(1):26–36. doi: 10.1021/bi00349a005. [DOI] [PubMed] [Google Scholar]
  9. Derse D., Cheng Y. C., Furman P. A., St Clair M. H., Elion G. B. Inhibition of purified human and herpes simplex virus-induced DNA polymerases by 9-(2-hydroxyethoxymethyl)guanine triphosphate. Effects on primer-template function. J Biol Chem. 1981 Nov 25;256(22):11447–11451. [PubMed] [Google Scholar]
  10. Derse D., Cheng Y. C. Herpes simplex virus type I DNA polymerase. Kinetic properties of the associated 3'-5' exonuclease activity and its role in araAMP incorporation. J Biol Chem. 1981 Aug 25;256(16):8525–8530. [PubMed] [Google Scholar]
  11. Drake J. W., Allen E. F., Forsberg S. A., Preparata R. M., Greening E. O. Genetic control of mutation rates in bacteriophageT4. Nature. 1969 Mar 22;221(5186):1128–1132. [PubMed] [Google Scholar]
  12. Fersht A. R. Fidelity of replication of phage phi X174 DNA by DNA polymerase III holoenzyme: spontaneous mutation by misincorporation. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4946–4950. doi: 10.1073/pnas.76.10.4946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frank K. B., Cheng Y. C. Inhibition of herpes simplex virus DNA polymerase by purine ribonucleoside monophosphates. J Biol Chem. 1986 Feb 5;261(4):1510–1513. [PubMed] [Google Scholar]
  14. Goscin L. P., Byrnes J. J. DNA polymerase delta: one polypeptide, two activities. Biochemistry. 1982 May 11;21(10):2513–2518. doi: 10.1021/bi00539a034. [DOI] [PubMed] [Google Scholar]
  15. Hall J. D., Furman P. A., St Clair M. H., Knopf C. W. Reduced in vivo mutagenesis by mutant herpes simplex DNA polymerase involves improved nucleotide selection. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3889–3893. doi: 10.1073/pnas.82.11.3889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hopfield J. J. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4135–4139. doi: 10.1073/pnas.71.10.4135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jovin T. M., Englund P. T., Bertsch L. L. Enzymatic synthesis of deoxyribonucleic acid. XXVI. Physical and chemical studies of a homogeneous deoxyribonucleic acid polymerase. J Biol Chem. 1969 Jun 10;244(11):2996–3008. [PubMed] [Google Scholar]
  18. Knopf K. W. Properties of herpes simplex virus DNA polymerase and characterization of its associated exonuclease activity. Eur J Biochem. 1979 Jul;98(1):231–244. doi: 10.1111/j.1432-1033.1979.tb13181.x. [DOI] [PubMed] [Google Scholar]
  19. Kunkel T. A., Beckman R. A., Loeb L. A. On the fidelity of DNA synthesis. Pyrophosphate-induced misincorporation allows detection of two proofreading mechanisms. J Biol Chem. 1986 Oct 15;261(29):13610–13616. [PubMed] [Google Scholar]
  20. Kunkel T. A., Loeb L. A. On the fidelity of DNA replication. The accuracy of Escherichia coli DNA polymerase I in copying natural DNA in vitro. J Biol Chem. 1980 Oct 25;255(20):9961–9966. [PubMed] [Google Scholar]
  21. Kunkel T. A., Schaaper R. M., Beckman R. A., Loeb L. A. On the fidelity of DNA replication. Effect of the next nucleotide on proofreading. J Biol Chem. 1981 Oct 10;256(19):9883–9889. [PubMed] [Google Scholar]
  22. Loeb L. A., Dube D. K., Beckman R. A., Koplitz M., Gopinathan K. P. On the fidelity of DNA replication. Nucleoside monophosphate generation during polymerization. J Biol Chem. 1981 Apr 25;256(8):3978–3987. [PubMed] [Google Scholar]
  23. Loeb L. A., Kunkel T. A. Fidelity of DNA synthesis. Annu Rev Biochem. 1982;51:429–457. doi: 10.1146/annurev.bi.51.070182.002241. [DOI] [PubMed] [Google Scholar]
  24. Masaki S., Koiwai O., Yoshida S. 10 S DNA polymerase alpha of calf thymus shows a microheterogeneity in its large polypeptide component. J Biol Chem. 1982 Jun 25;257(12):7172–7177. [PubMed] [Google Scholar]
  25. Muzyczka N., Poland R. L., Bessman M. J. Studies on the biochemical basis of spontaneous mutation. I. A comparison of the deoxyribonucleic acid polymerases of mutator, antimutator, and wild type strains of bacteriophage T4. J Biol Chem. 1972 Nov 25;247(22):7116–7122. [PubMed] [Google Scholar]
  26. Ninio J. Kinetic amplification of enzyme discrimination. Biochimie. 1975;57(5):587–595. doi: 10.1016/s0300-9084(75)80139-8. [DOI] [PubMed] [Google Scholar]
  27. Nishiyama Y., Maeno K., Yoshida S. Characterization of human cytomegalovirus-induced DNA polymerase and the associated 3'-to-5', exonuclease. Virology. 1983 Jan 30;124(2):221–231. doi: 10.1016/0042-6822(83)90339-2. [DOI] [PubMed] [Google Scholar]
  28. Nishiyama Y., Suzuki S., Yamauchi M., Maeno K., Yoshida S. Characterization of an aphidicolin-resistant mutant of herpes simplex virus type 2 which induces an altered viral DNA polymerase. Virology. 1984 May;135(1):87–96. doi: 10.1016/0042-6822(84)90119-3. [DOI] [PubMed] [Google Scholar]
  29. Nishiyama Y., Yoshida S., Tsurumi T., Yamamoto N., Maeno K. Drug-resistant mutants of herpes simplex virus type 2 with a mutator or antimutator phenotype. Microbiol Immunol. 1985;29(4):377–381. doi: 10.1111/j.1348-0421.1985.tb00837.x. [DOI] [PubMed] [Google Scholar]
  30. Scheuermann R. H., Echols H. A separate editing exonuclease for DNA replication: the epsilon subunit of Escherichia coli DNA polymerase III holoenzyme. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7747–7751. doi: 10.1073/pnas.81.24.7747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Silber J. R., Fry M., Martin G. M., Loeb L. A. Fidelity of DNA polymerases isolated from regenerating liver chromatin of aging Mus musculus. J Biol Chem. 1985 Jan 25;260(2):1304–1310. [PubMed] [Google Scholar]
  32. Slater J. P., Tamir I., Loeb L. A., Mildvan A. S. The mechanism of Escherichia coli deoxyribonucleic acid polymerase I. Magnetic resonance and kinetic studies of the role of metals. J Biol Chem. 1972 Nov 10;247(21):6784–6794. [PubMed] [Google Scholar]
  33. Weymouth L. A., Loeb L. A. Mutagenesis during in vitro DNA synthesis. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1924–1928. doi: 10.1073/pnas.75.4.1924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yoshida S., Suzuki R., Masaki S., Koiwai O. DNA primase associated with 10 S DNA polymerase alpha from calf thymus. Biochim Biophys Acta. 1983 Dec 22;741(3):348–357. doi: 10.1016/0167-4781(83)90155-0. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES