The inhibition of mitochondrial DNA polymerase {alpha} from animal cells by intercalating drugs

DNA polymerase λ from purified nuclei of EMT-6 cells (mice) seems to be identical to the mitochondrial DNA polymerase from the same source following several criteria. These two enzyme activities are strongly inhibited by ethidium bromide and acriflavin, while proflavin, acridine orange, daunomycin and ohioroquine inhibition is less pronounced. In the case of DNA polymerases α and β very little inhibition by ethidiuni bromide was observed. Intercalation of this dye in a poly dA-dT<inf>12–18</inf> template-primer was studied spectrophotometrically under conditions simitar to those in the <unl>in vitro</unl> DNA polymerase assay. The inhibition by this drug of the mitochondrial DNA polymerase y activity was shown to be competitive at varying concentrations of TTP while the inhibition was of the non-competitive type at different concentrations of poly dA-dT<inf>12–18</inf> We conclude that the drug, most probably in the intercalated form, is ab'e to interact with the active site (s) of mitochondrial DNA polymerase.