Inhibition of DNA polymerase alpha by 2',3'-dideoxyribonucleoside 5'-triphosphates: effect of manganese ion. 1984

K Ono, and M Ogasawara, and Y Iwata, and H Nakane

Inhibitory effects of 2',3'-dideoxyribonucleoside 5'-triphosphates (ddNTP's) on the activity of mouse myeloma DNA polymerase alpha were examined. In contrast to the widely accepted conclusion that DNA polymerase alpha was not inhibited by ddNTP, our results showed that all 4 ddNTP's (ddATP, ddCTP, ddGTP, ddTTP) exhibited strong inhibitory power to this enzyme in the presence of Mn2+. The observed inhibitions by ddNTP's were neither due to chain termination of growing DNA nor to enzyme inactivation by these compounds, but due to competition with deoxynucleoside triphosphate with the same base. The inhibition constant (Ki) varied depending on the combination of template-primer, substrate and inhibitor. The results suggest that Mn2+ plays a role in increasing affinity of the dideoxynucleotides to DNA polymerase alpha by interacting with anyone or more of the dideoxynucleotide, enzyme and template-primer.

UI MeSH Term Description Entries
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)
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
D003854 Deoxyribonucleotides A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group. Deoxyribonucleotide
D004257 DNA Polymerase II A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. DNA Polymerase epsilon,DNA-Dependent DNA Polymerase II,DNA Pol II,DNA Dependent DNA Polymerase II
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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