Effects of DNA Polymerase Inhibitors on Replicative and Repair DNA Synthesis in Ultraviolet-irradiated HeLa Cells

SummaryAphidicolin specifically inhibits eukaryotic DNA polymerase α, while 2′,3′-dideoxythymidine 5′-triphosphate (d2TTP) inhibits DNA polymerase β and γ but not α. 1-β-D-Arabinofuranosylcytosine 5′-triphosphate (araCTP) inhibits both DNA polymerase α and β although to a different extent. Here we measured the effects of these inhibitors on repair DNA synthesis of U.V.-irradiated HeLa cells by two different methods. Firstly, aphidicolin, 1-β-D-arabinofuranosylcytosine (araC, a precursor of araCTP) and 2′,3′-dideoxythimidine (d2Thd, a precursor of d2TTP) were added directly to the culture medium. In this case, aphidicolin and araC strongly inhibited replicative DNA synthesis of HeLa cells, and they also inhibited repair synthesis after U.V.-irradiation but to a much lesser extent. In contrast, high concentrations of d2Thd inhibited repair DNA synthesis to a higher extent than replicative DNA synthesis. Secondly, the active form of inhibitor, d2TTP, was microinjected directly into cytoplasm or nuclei or U.V...