Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1970 Jul;66(3):823–829. doi: 10.1073/pnas.66.3.823

Suppression of Chemical Mutagenesis in Bacteriophage T4 by Genetically Modified DNA Polymerases*

John W Drake 1, Elaine O Greening 1
PMCID: PMC283124  PMID: 5269245

Abstract

Two antimutagenic DNA polymerases of bacteriophage T4 markedly reduce transition mutagenesis by a variety of chemical mutagens. Spontaneous mutation and mutagenesis by 2-aminopurine, 5-bromodeoxyuridine, and thymine deprivation are strongly suppressed. Mutagenesis at G:C sites by ethyl methanesulfonate, and at A:T sites by nitrous acid, is moderately suppressed. Mutagenesis at G:C sites by hydroxylamine and by nitrous acid is not suppressed. These results support the notion that the indispensable DNA polymerase of bacteriophage T4 plays a crucial role in the selection of the correct base during DNA replication. The data also reveal that mutagenic specificities of chemical agents depend as much upon the characteristics of the enzymatic apparatus of DNA replication as they do upon the chemistry of primary mutational lesions.

Full text

PDF
825

Selected References

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

  1. Baldy M. W. Repair and recombination in phage T4. II. Genes affecting UV sensitivity. Cold Spring Harb Symp Quant Biol. 1968;33:333–338. doi: 10.1101/sqb.1968.033.01.038. [DOI] [PubMed] [Google Scholar]
  2. De Lucia P., Cairns J. Isolation of an E. coli strain with a mutation affecting DNA polymerase. Nature. 1969 Dec 20;224(5225):1164–1166. doi: 10.1038/2241164a0. [DOI] [PubMed] [Google Scholar]
  3. De Waard A., Paul A. V., Lehman I. R. The structural gene for deoxyribonucleic acid polymerase in bacteriophages T4 and T5. Proc Natl Acad Sci U S A. 1965 Oct;54(4):1241–1248. doi: 10.1073/pnas.54.4.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drake J. W., Allen E. F. Antimutagenic DNA polymerases of bacteriophage T4. Cold Spring Harb Symp Quant Biol. 1968;33:339–344. doi: 10.1101/sqb.1968.033.01.039. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Drake J. W. Comparative rates of spontaneous mutation. Nature. 1969 Mar 22;221(5186):1132–1132. doi: 10.1038/2211132a0. [DOI] [PubMed] [Google Scholar]
  7. Drake J. W., McGuire J. Characteristics of mutations appearing spontaneously in extracellular particles of bacteriophage T4. Genetics. 1967 Mar;55(3):387–398. doi: 10.1093/genetics/55.3.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drake J. W. Spontaneous mutations accumulating in bacteriophage T4 in the complete absence of DNA replication. Proc Natl Acad Sci U S A. 1966 Apr;55(4):738–743. doi: 10.1073/pnas.55.4.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freese E. B., Freese E. On the specificity of DNA polymerase. Proc Natl Acad Sci U S A. 1967 Mar;57(3):650–657. doi: 10.1073/pnas.57.3.650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goulian M., Lucas Z. J., Kornberg A. Enzymatic synthesis of deoxyribonucleic acid. XXV. Purification and properties of deoxyribonucleic acid polymerase induced by infection with phage T4. J Biol Chem. 1968 Feb 10;243(3):627–638. [PubMed] [Google Scholar]
  11. Gross J., Gross M. Genetic analysis of an E. coli strain with a mutation affecting DNA polymerase. Nature. 1969 Dec 20;224(5225):1166–1168. doi: 10.1038/2241166a0. [DOI] [PubMed] [Google Scholar]
  12. Kornberg A. Active center of DNA polymerase. Science. 1969 Mar 28;163(3874):1410–1418. doi: 10.1126/science.163.3874.1410. [DOI] [PubMed] [Google Scholar]
  13. Speyer J. F., Karam J. D., Lenny A. B. On the role of DNA polymerase in base selection. Cold Spring Harb Symp Quant Biol. 1966;31:693–697. doi: 10.1101/sqb.1966.031.01.088. [DOI] [PubMed] [Google Scholar]
  14. Speyer J. F. Mutagenic DNA polymerase. Biochem Biophys Res Commun. 1965 Oct 8;21(1):6–8. doi: 10.1016/0006-291x(65)90417-1. [DOI] [PubMed] [Google Scholar]
  15. Speyer J. F., Rosenberg D. The function of T4 DNA polymerase. Cold Spring Harb Symp Quant Biol. 1968;33:345–350. doi: 10.1101/sqb.1968.033.01.040. [DOI] [PubMed] [Google Scholar]
  16. Warner H. R., Barnes J. E. Deoxyribonucleic acid synthesis in Escherichia coli infected with some deoxyribonucleic acid polymerase-less mutants of bacteriophage T4. Virology. 1966 Jan;28(1):100–107. doi: 10.1016/0042-6822(66)90310-2. [DOI] [PubMed] [Google Scholar]
  17. Wolfenden R. V. Tautomeric equilibria in inosine and adenosine. J Mol Biol. 1969 Mar 14;40(2):307–310. doi: 10.1016/0022-2836(69)90479-3. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES