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Nucleic Acids Research, 1981, Vol. 9, No. 18 4709-4719
© 1981


MOLECULAR BIOLOGY

Aphidicolin inhibits DNA synthesis by DNA polymerase {alpha} and isolated nuclei by a similar mechanism

Hans Krokan, Erik Wist and Ruth Haaland Krokan

Institute of Medical Biology, University of Tromsø 9000 Tromsø, Norway

Received June 30, 1981. 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.


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