Inhibition cyclic guanosine 3':5'-monophosphate of the soluble DNA polymerase activity, and of partially purified DNA polymerase A (DNA polymerase I) from the yeast Saccharomyces cerevisiae.
DNA polymerase activity from extracts of growing yeast cells is inhibited by cGMP. Experiments with partially purified yeast DNA polymerases show, that cGMP inhibits DNA polymerase A (DNA polymerase I from Chang), which is the main component of the soluble DNA polymerase activity in yeast extracts, by competing for the enzyme with the primer-template DNA. Since the enzyme is not only inhibited by 3', 5'-cGMP, but also by 3',5'-cAMP, the 3'--:5'-phosphodiester seems to be crucial for the competition between cGMP and primer. This would be inconsistent with the concept of a 3'-OH primer binding site in the enzyme. The existence of such a site in the yeast DNA polymerase A is indicated from studies with various purine nucleoside monophosphates. When various DNA polymerases are compared, inhibition by cGMP seems to be restricted to those enzymes, which are involved in DNA replication, DNA polymerases with an associated nuclease activity are not inhibited, DNA polymerase B from yeast is even activated by cGMP. Though some relations between the cGMP effect and the presumed function of the enzymes in the living cell are apparent, the biological meaning of the observations in general remains open.
D000818:Animals; D002417:Cattle; D006152:Cyclic GMP / Q000494:pharmacology*; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D004257:DNA Polymerase II / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004622:Embryo, Mammalian; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D019384:Nucleic Acid Synthesis Inhibitors; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013045:Species Specificity; D013806:Theophylline / Q000494:pharmacology
D019384:Nucleic Acid Synthesis Inhibitors; D013806:Theophylline; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D006152:Cyclic GMP