On the inhibition of the RNA polymerase-catalysed synthesis of RNA by daunomycin. Interference of the inhibitor with elongation and pre-longation steps.

The inhibition of the RNA polymerase-catalyzed synthesis of RNA by daunomycin was examined. Saturation binding of daunomycin to the template leads, as expected, to complete inhibition of RNA synthesis as a result of daunomycin interference with enzyme-template interactions. However at concentrations of the inhibitor below saturation formation of the enzyme-template complex remains remarkably undisturbed, while both the transformation of this complex to an elongating complex and the elongation of the nacsent RNA chains are substantially inhibited. Clearly, daunomycin interferes with a number of different substeps of RNA synthesis and inhibits the synthesis by different mechanisms depending on the amount of inhibitor bound to the template. Elucidation of the mechanism of inhibition at low daunomycin concentrations may be a prerequisite for a better understanding of the mechanism of the pharmacological action of the drug.