Open AccessAphidicolin inhibits DNA synthesis by DNA polymerase α and isolated nuclei by a similar mechanism
Author(s) -
Hans E. Krokan,
Erik Wist,
Ruth Haaland Krokan
Publication year - 1981
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/9.18.4709
Subject(s) - aphidicolin , biology , dna polymerase , dna synthesis , dna , polymerase , microbiology and biotechnology , mechanism of action , hela , dna replication , dna polymerase ii , biochemistry , biophysics , cell , polymerase chain reaction , in vitro , gene , reverse transcriptase
Aphidicolin is a selective inhibitor of DNA polymerase alpha. In contrast to earlier reports, the drug was found to inhibit DNA synthesis catalyzed by DNA polymerase alpha and isolated HeLa cell nuclei by a similar mechanism. For both systems aphidicolin primarily competed with dCTP incorporation. However, the apparent Vmax for dCTP incorporation was reduced by 50-60% at relatively low concentrations of aphidicolin, thus the mechanism of inhibition is complex. Furthermore, a 2-5 fold increase in apparent Km for dTTP was observed in the presence of aphidicolin, but the apparent Km values for dATP and dGTP were essentially unaltered. This, together with additional evidence, suggested that the mechanism of action of aphidicolin involves a strong competition with dCMP incorporation, a weaker competition with dTMP incorporation and very little, if any, competition with dGMP and dAMP incorporation.