Abstract
We describe in vitro measurements of heteroduplex base mispaired intermediates involving 5-bromouracil and 2-aminopurine in A·T → G·C and G·C → A·T transition mutation pathways. For the case of 2-amino- purine, 2-aminopurine·cytosine mispairs are formed at a much higher frequency than adenine·cytosine mispairs in either transition pathway. For the case of 5-bromouracil, at least a 40-fold increase in 5-bromouracil-guanine mispairs are observed over thymine·guanine mispairs but only in the A·T → G·C pathway. In the A·T → G·C pathway, mispairs involving 5-bromouracil are formed 2.5-fold more frequently to those involving thymine suggesting perhaps that 5-bromouracil may exhibit substantially different base-pairing behavior depending on whether it is present as a template base or as a deoxyribonucleosides triphosphate substrate. The effect of the base analogs on dNTP pool size perturbations is discussed. A measurement of dNTP pools in 2-aminopurine mutagenized bacteriophage T4-infected cells is presented. An approximate eight-fold expansion in common dNTP pools is observed in a ts L141 antimutator genetic background compared to wild type T4 43+ and ts L56 mutator backgrounds. The effects of distorted dNTP pools on mutagenesis will be considered.
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References
C. R. Ashman and R. L. Davison, Bromodeoxyuridine Mutagenesis in Mammalian Cells is Related to Deoxynucleotide Pool Imbalance, Mol. Cell. Biol., 1: 254–260 (1981).
S. Benzer, On the Topography of the Genetic Fine Structure, Proc. Natl. Acad. Sci., U.S.A., 45: 1607–1620 (1959).
M. J. Bessman, I. R. Lehman, J. A. Adler, S. B. Zimmerman, E. S. Simms, and A. Kornberg, Enzymatic Synthesis of Deoxy- nucleic Acid. III. The Incorporation of Pyrimidine and Purine Analogs into Deoxynucleic Acid, Proc. Natl. Acad. Sci., 44: 633–640 (1958).
M. J. Bessman, N. Muzyczka, M. F. Goodman, and R. L. Schnaar, Studies on the Biochemical Basis of Spontaneous Mutation. II. The Incorporation of a Base and Its Analog into DNA by Wild- Type, Mutator, and Antimutator DNA Polymerases, J. Mol. Biol., 88: 409–421 (1974).
S. P. Champe and S. Benzer, Reversal of Mutant Phenotypes by Fluorouracil: An Approach to Nucleotide Sequences in Messenger RNA, Proc. Natl. Acad. Sci., U.S.A., 48: 532–546 (1962).
L. M. S. Chang and F. J. Bollum, Deoxynucleotide-Polymerizing Enzymes of Calf Thymus Gland, J. Biol. Chem., 246: 909–916 (1971).
L. K. Clayton, M. F. Goodman, E. W. Branscomb, and D. J. Galas, Error Induction and Correction by Mutant and Wild Type T4 DNA Polymerase, J. Biol. Chem., 254: 1902–1912 (1979).
C. Coulondre, J. H. Miller, P. J. Farabaugh, and W. Gilbert, Molecular Basis of Base Substitution Hotspots, In Escherichia coli, Nature, 274:775–780 (1979).
W. Drake, Comparative Rates of Spontaneous Mutation, Nature, 221: 1132 (1969).
J. W. Drake, The Molecular Basis of Mutation, Holden-Day, San Francisco (1970).
A. R. Fersht, Fidelity of Replication of Phage ⌽X174 DNA by DNA Polymerase III Holoenzyme: Spontaneous Mutation by Mis- incorporation, PNAS U.S.A., 76: 4946–4950 (1979).
A. Fersht, J. W. Knill-Jones, and W. C. Tsui, Kinetic Basis of Spontaneous Mutations Misertion Frequencies, Proofreading Specificities and Cost of Proofreading by DNA Polymerases of E. coli, J. Mol. Biol., 156: 37–51 (1982).
E. Freese, The Specific Mutagenic Effect of Base Analogs on Phage T4, J. Mol. Biol., 1: 87–105 (1959).
C. Garret and D. V. Santi, A Rapid and Sensitive High Pressure Liquid Chromatography Assay for Deoxyribonucleoside Triphosphates in Cell Extracts, Analyt. Biochem., 99: 268–273 (1979).
M. F. Goodman and E. W. Branscomb, DNA Replication Fidelity and Base Mispairing Mutagenesis: Relating Experiments to a Km Discrimination DNA Polymerase Model, in: “Accuracy in Molecular Biology” (D. J. Galas, ed.), Marcel Dekker, to be published (1984).
M. F. Goodman, R. Hopkins, and W. C. Gore, 2-Aminopurine-induced Mutagenesis in T4 Bacteriophage: A Model Relating Mutation Frequency to 2-Aminopurine Incorporation in DNA, Proc. Natl. Acad. Sci., U.S.A., 74: 4806–4810 (1977).
M. F. Goodman and R. L. Ratliff, Evidence of 2-Aminopurine* cytosine Base Pairing Involving 2 Hydrogen Bonds: A 2-Amino- purine Tautomer? Submitted for publication (1983).
R. Hopkins and M. F. Goodman, Assymmetry in Forming 2-Amino- purine ’hydroxymethylcy to sine Heteroduplexes; A Model Giving Misincorporation Frequencies and Rounds of DNA Replication from Base-Pair Populations in vivo, J. Mol. Biol., 135: 1–22 (1979).
R. Hopkins and M. F. Goodman, Deoxyribonucleotide Pools, Base Pairing and Sequence Configuration Affecting Bromodeoxyuridine- and 2-Aminopurine-Induced Mutagenesis, Proc. Natl. Acad. Sci., U.S.A., 77: 1801–1805 (1980).
R. B. Innman and R. L. Baldwin, Helix-Random Coil Transitions in DNA Homopolymer Pairs, J. Biol. Chem., 8: 452–469 (1964).
E. R. Kaufman and R. L. Davidson, Bromodeoxyuridine Mutagenesis in Mammalian Cells: Mutagenesis is Independent of the Amount of Bromouracil in DNA, Proc. Natl. Acad. Sci., 75: 4982–4986 (1978).
E. R. Kaufman and R. L. Davidson, Bromodeoxyuridine Mutagenesis in Mammalian Cells: Mutagenesis is Independent of the Amount of Bromouracil in DNA, Proc. Natl. Acad. Sci., 75: 4982–4986 (1978).
C. K. Mathews, Biochemistry of Deoxyribonucleic Acid-Defective Amber Mutants of Bacteriphage T4. (Ill Nucleotide Pools), The J. of Biol. Chem., 247: 7430–7438 (1972).
M. Meuth and H. Green, Alterations Leading to Increased Ribonucleotide Reductase in Cells Selected for Resistance to Deoxy- nucleosides, Cell, 3: 367–374 (1974).
M. Meuth and H. Green, Alterations Leading to Increased Ribonucleotide Reductase in Cells Selected for Resistance to Deoxy- nucleosides, Cell, 3: 367–374 (1974).
C. F. Morris, H. Hammar-Inaba, D. Mare, N. K. Sinha, and B. Alberts, Purification of the Gene 43, 44, 45, and 62 Proteins of the Bacteriophage T4 DNA Replication Apparatus, J. Biol. Chem., 254: 6787–6796 (1979).
N. Muzyczka, R. L. Poland, and M. J. Bessman, 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., 247: 7116–7122 (1972).
L. S. Ripley, The Influence of Diverse Gene 43 DNA Polymerases on the Insertion and Replication in vivoof 2-Aminopurine at A-T BaSe Pairs in Bacteriophage T4, J. Mol. Biol., 150: 197–216 (1981).
A. Ronen, 2-Aminopurine, Mutat. Res., 69: 1–47 (1979).
A. Ronen and A. Rahat, Mutagen Specificity and Position Effects on Mutation T4 rji Nonsense Sites, Mutation Rev., 34: 21–34 (1976).
B. Rydberg, Bromouracil Mutagenesis and Mismatch Repair in Mutator Strains of Escherichia coli, Mutat. Res., 52: 11–24 (1978).
T. R. Skopek and F. Hutchinson, DNA Base Sequence Changes Induced by Bromouracil Mutagenesis of Lambda Phage, J. Mol. Biol., 159: 19–33 (1982).
L. Thelander and P. Reichard, Reduction of Ribonucleotides, Ann. Rev. Biochem., 48: 133 - 158 (1979).
T. A. Trautner, M. N. Swartz, and A. Romberg, Enzymatic Synthesis of Deoxyribonucleic Acid, X. Influence of Bromouracil Substitutions on Replication, Proc. Natl. Acad. Sci. U.S.A., 48: 449–455 (1962).
S. M. Watanabe and M. F. Goodman, On the Molecular Basis of Transition Mutations: The Frequencies of Forming and 2-Amino- purine • cy to sine Adene«cytosine Base Mispairs in vitro, Proc. Natl. Acad. Sci., U.S.A., 78: 2864–2868 (1981).
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© 1985 Plenum Press, New York
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Goodman, M.F., Hopkins, R.L., Lasken, R., Mhaskar, D.N. (1985). The Biochemical Basis of 5-Bromouracil- and 2-Aminopurine-Induced Mutagenesis. In: de Serres, F.J. (eds) Genetic Consequences of Nucleotide Pool Imbalance. Basic Life Sciences, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2449-2_25
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DOI: https://doi.org/10.1007/978-1-4613-2449-2_25
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