On the fidelity of DNA replication. Effect of metal activators during synthesis with avian myeloblastosis virus DNA polymerase

J Biol Chem. 1977 Jun 10;252(11):3605-10.


The effect of metal activators on the fidelity of DNA synthesis has been examined. Using the DNA polymerase from avian myeloblastosis virus, the accuracy of Co2+-, M2+-, and Ni2+-activated DNA synthesis was determined with different polynucleotide templates. With poly[d(A-T)] as the template, the error frequency for dCMP incorporation was 1:1400, 1:1100, and 1:600 for Mg2+, Co2+, and Mn2+, respectively, at maximally activating concentrations. The error frequency was invariant with respect to [Mg2+] but increased with greater than activating concentrations of Co2+ and Mn2+. This increase resulted from differential rates of complementary and noncomplementary nucleotide incorporation. The enhanced error frequency was nonspecific as it occurred with all polynucleotide templates and with all noncomplementary deoxy- and ribonucleotides which were tested. Nearest neighbor analyses of the reaction products indicated that the noncomplementary deoxynucleotides were incorporated as single base substitutions. The fidelity of Ni2+-activated DNA synthesis was invariant with respect to [Ni2+] and was similar to that obtained using Mg2+. During DNA synthesis with Mg2+, the addition of Co2+, Mn2+, or Ni2+ resulted in a decrease in the fidelity of DNA synthesis. The relationship between decreases in the fidelity of DNA synthesis and metal mutagenesis, or carcinogenesis, or both, is considered.

MeSH terms

  • Avian Myeloblastosis Virus
  • Cations, Divalent / pharmacology*
  • Cobalt / pharmacology
  • DNA / biosynthesis*
  • DNA Replication / drug effects*
  • DNA-Directed DNA Polymerase / metabolism*
  • Guanine Nucleotides
  • Magnesium / pharmacology
  • Manganese / pharmacology
  • Nickel / pharmacology
  • Oligodeoxyribonucleotides
  • Poly C
  • Poly dA-dT / metabolism
  • Templates, Genetic
  • Thymus Gland


  • Cations, Divalent
  • Guanine Nucleotides
  • Oligodeoxyribonucleotides
  • Poly dA-dT
  • Poly C
  • Cobalt
  • Manganese
  • Nickel
  • DNA
  • DNA-Directed DNA Polymerase
  • Magnesium