INTERACTION OF HUMAN DNA POLYMERASE-BETA WITH IONS OF COPPER, LEAD, AND CADMIUM

Under appropriate conditions, divalent copper, lead, and cadmium ions significantly inhibit human DNA polymerase β (following accepted convention, the term DNA polymerase β refers to the low-molecular-weight, 3-4 S DNA polymerase of eukaryotic cells) at concentrations below 10-5 m. Each metal showed apparent linear noncompetitive inhibition kinetics with respect to the template primer and the deoxynucleoside triphosphate substrate, indicating that complex formation with these components does not account for the inhibition. Apparently, neither lead nor cadmium inhibit by displacing required zinc atoms from the polymerase. The interaction of the metals with the enzyme can be reversed or prevented by EDTA or by thiol compounds, except that inhibition by cadmium ions can be reversed by monothiols but not by dithiols. The metals probably do not inhibit through reaction with thiol groups since the inhibition is not decreased by pretreating the enzyme with N-ethylmaleimide. Although divalent zinc is moderately inhibitory in manganese activated poly(dT) synthesis on a poly(dA) template, it can fill the requirement for a divalent metal ion and, under the conditions tested, is about 60% as effective as Mn2+. © 1979.