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PMID: 270713 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

2-Aminopurine-induced mutagenesis in T4 bacteriophage: a model relating mutation frequency to 2-aminopurine incorporation in DNA.

Goodman MF, Hopkins R, Gore WC

Abstract

We measured the in vivo incorporation of 2-aminopurine into DNA of T4 bacteriophage allelic for gene 43 (DNA polymerase), mutator (L56), 43+, and antimutator (L141). The magnitude of incorporation (mol/mol of Thy) was 1/1500 in L56, 1/1600 in 43+, and 1/8900 in L141. The incorporation ratio L56:43+:L141 in vivo was equal to that mediated by the purified DNA polymerases of these allelic phages in vitro. A model for 2-aminopurine-induced A-T in equilibrium G-C transitions is discussed. The model is used to predict the magnitudes of replication errors (C mispairing with a template 2-aminopurine) and incorporation errors (2-aminopurine mispairing with a template C) per round of replication and to investigate the asymmetry in 2-aminopurine-induced transitions favoring the A-T leads to G-C pathway over G-C leads to A-T. We suggest that the fidelity of L56 and L141 DNA polymerases exemplifies one-step and two-step editing, respectively.

MeSH Terms
2-Aminopurine/pharmacology Adenine/analogs & derivatives Aminopyrine/metabolism Coliphages/drug effects,genetics DNA, Viral/biosynthesis Models, Biological Mutagens
Chemicals
DNA, Viral Mutagens Aminopyrine 2-Aminopurine Adenine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Goodman M F
Hopkins R
Gore W C
References (19)
19 references, click to expand
  1. Mutator mutations in bacteriophage T4 gene 32 (DNA unwinding protein).
    J Virol. 1976 Aug;19(2):490-4 PMID: 957480
  2. Complementary base pairing and the origin of substitution mutations.
    Nature. 1976 Sep 23;263(5575):285-9 PMID: 958482
  3. 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):241-8 PMID: 4336040
  4. 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):4135-9 PMID: 4530290
  5. 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):7116-22 PMID: 4565077
  6. On the role of deoxyribonucleic acid polymerase in determining mutation rates. Characterization of the defect in the T4 deoxyribonucleic acid polymerase caused by the ts L88 mutation.
    J Biol Chem. 1973 Feb 25;248(4):1417-23 PMID: 4568816
  7. Studies on the biochemical basis of spontaneous mutation. II. The incorporation of a base and its analogue into DNA by wild-type, mutator and antimutator DNA polymerases.
    J Mol Biol. 1974 Sep 15;88(2):409-21 PMID: 4616089
  8. The function of T4 DNA polymerase.
    Cold Spring Harb Symp Quant Biol. 1968;33:345-50 PMID: 4891974
  9. Genetic control of mutation rates in bacteriophageT4.
    Nature. 1969 Mar 22;221(5186):1128-32 PMID: 4975273
  10. The structural gene for deoxyribonucleic acid polymerase in bacteriophages T4 and T5.
    Proc Natl Acad Sci U S A. 1965 Oct;54(4):1241-8 PMID: 5219829
  11. On the role of DNA polymerase in base selection.
    Cold Spring Harb Symp Quant Biol. 1966;31:693-7 PMID: 5237208
  12. Antimutagenic DNA polymerases of bacteriophage T4.
    Cold Spring Harb Symp Quant Biol. 1968;33:339-44 PMID: 5254574
  13. The influence of neighboring base pairs upon base-pair substitution mutation rates.
    Proc Natl Acad Sci U S A. 1971 Apr;68(4):773-6 PMID: 5279518
  14. Properties of bacteriophage T4 mutants defective in DNA polymerase.
    Genetics. 1970 Jun;65(2):187-200 PMID: 5474826
  15. The mutagenic effect of hydroxyaminopurine derivatives on phage T4.
    Mutat Res. 1968 Mar-Apr;5(2):299-301 PMID: 5672975
  16. A determination of mutagen specificity in bacteria using nonsense mutants of bacteriophage T4.
    J Mol Biol. 1967 Jun 28;26(3):437-47 PMID: 6029739
  17. Mutation as an error in base pairing.
    Biochem Biophys Res Commun. 1960 Sep;3:275-80 PMID: 13744470
  18. Reversal of mutant phenotypes by 5-fluorouracil: an approach to nucleotide sequences in messenger-RNA.
    Proc Natl Acad Sci U S A. 1962 Apr 15;48:532-46 PMID: 13877975
  19. On the specificity of DNA polymerase.
    Proc Natl Acad Sci U S A. 1967 Mar;57(3):650-7 PMID: 16591513
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1977-11-00
Pages
4806-10
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC432044
Subset
IM
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