Quinolone antibiotics inhibit eucaryotic DNA polymerase alpha and beta, terminal deoxynucleotidyl transferase but not DNA ligase.
DNA polymerases alpha and beta, Terminal deoxynucleotidyl Transferase and DNA ligases from chicken thymus were purified to homogeneity. Quinolone antibiotics (nalidixic acid, oxolinic acid and pefloxacin ) known to inhibit DNA replication were tested for their effects on these enzymes. DNA ligase activity was not affected by the three drugs. DNA polymerases alpha and beta were inhibited by competitive mechanisms. Surprisingly, Terminal deoxynucleotidyl Transferase was strongly inhibited by the three compounds and more efficiently by nalidixic acid. The significance of these results is discussed in terms of the possible involvement of the enzymes in the respective DNA replication and repair processes.
D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000494:pharmacology*; D002645:Chickens; D011088:DNA Ligases / Q000378:metabolism*; D004253:DNA Nucleotidylexotransferase / Q000037:antagonists & inhibitors*; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D009268:Nalidixic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors; D010093:Oxolinic Acid / Q000494:pharmacology; D015366:Pefloxacin; D011118:Polynucleotide Ligases / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D013950:Thymus Gland / Q000201:enzymology
D000892:Anti-Infective Agents, Urinary; D019384:Nucleic Acid Synthesis Inhibitors; D011804:Quinolines; D015366:Pefloxacin; D009268:Nalidixic Acid; D004254:DNA Nucleotidyltransferases; D004253:DNA Nucleotidylexotransferase; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D011088:DNA Ligases; D011118:Polynucleotide Ligases; D010093:Oxolinic Acid