Biomaterial Database

On the fidelity of DNA replication. Effect of metal activators during synthesis with avian myeloblastosis virus DNA polymerase. 1977

M A Sirover, and L A Loeb

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.

UI	MeSH Term	Description	Entries
D008274	Magnesium	A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008345	Manganese	A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
D009189	Avian Myeloblastosis Virus	A species of ALPHARETROVIRUS causing anemia in fowl.	Myeloblastosis Virus, Avian,Avian Myeloblastosis Viruses,Myeloblastosis Viruses, Avian,Virus, Avian Myeloblastosis,Viruses, Avian Myeloblastosis
D009532	Nickel	A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme UREASE.
D009838	Oligodeoxyribonucleotides	A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.	Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D011066	Poly C	A group of cytosine ribonucleotides in which the phosphate residues of each cytosine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.	Cytosine Polynucleotides,Polycytidylic Acid,Polycytidylic Acids,Acid, Polycytidylic,Acids, Polycytidylic,Polynucleotides, Cytosine
D011067	Poly dA-dT	Polydeoxyribonucleotides made up of deoxyadenine nucleotides and thymine nucleotides. Present in DNA preparations isolated from crab species. Synthetic preparations have been used extensively in the study of DNA.	Poly(Deoxyadenylate-Thymidylate),Polydeoxyadenine Nucleotides-Polythymine Nucleotides,Poly dA dT,Poly(dA-dT),d(A(5)T(5))2,Nucleotides, Polydeoxyadenine Nucleotides-Polythymine,Nucleotides-Polythymine Nucleotides, Polydeoxyadenine,Polydeoxyadenine Nucleotides Polythymine Nucleotides,dA dT, Poly,dA-dT, Poly,dT, Poly dA
D002413	Cations, Divalent	Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.	Divalent Cations
D003035	Cobalt	A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.	Cobalt-59,Cobalt 59
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA