title: On the fidelity of DNA replication. Effect of metal activators during synthesis with avian myeloblastosis virus DNA polymerase.
abstract: 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: D009189:Avian Myeloblastosis Virus; D002413:Cations, Divalent / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006150:Guanine Nucleotides; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides; D011066:Poly C; D011067:Poly dA-dT / Q000378:metabolism; D013698:Templates, Genetic; D013950:Thymus Gland
chemical_list: D002413:Cations, Divalent; D006150:Guanine Nucleotides; D009838:Oligodeoxyribonucleotides; D011067:Poly dA-dT; D011066:Poly C; D003035:Cobalt; D008345:Manganese; D009532:Nickel; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D008274:Magnesium