Differential susceptibilities of DNA polymerases-alpha and -beta to polyanions.
The effects of various polyanions including synthetic polynucleotides on DNApolymerases-alpha and -beta from blastulae of the sea urchin Hemicentrotus pulcherrimus and HeLa cells were studied. Only DNA polymerase-alpha was inhibited by polyanions, such as polyvinyl sufate, dextran sulfate, heparin, poly(G), poly(I), poly(U) and poly(ADP-Rib). Of the various polynucleotides tested, poly(G) and poly(I) were the strongest inhibitors. Kinetic studies showed that the Ki value for poly(G) was 0.3 microgram/ml and that poly(G) had 20-fold higher affinity than activated DNA for the template-primer site of DNA polymerase-alpha. Poly(U) and poly(ADP-Rib) were also inhibitory, but they were one hundredth as inhibitory as poly(G) or poly(I). Poly(A), poly(C), poly(A).poly(U) AND POLY(I).poly(C) were not inhibitory to DNA polymerase-alpha. In contrast, DNA olymerase-beta was not affected at all by these polyanions under the same conditions.
D000818:Animals; D000838:Anions / Q000494:pharmacology; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D007700:Kinetics; D019384:Nucleic Acid Synthesis Inhibitors; D011064:Poly Adenosine Diphosphate Ribose / Q000494:pharmacology; D011131:Polyribonucleotides / Q000494:pharmacology; D012617:Sea Urchins / Q000201:enzymology
D000838:Anions; D019384:Nucleic Acid Synthesis Inhibitors; D011131:Polyribonucleotides; D011064:Poly Adenosine Diphosphate Ribose