Inhibition of DNA polymerase alpha activity by proteins from rat liver.
We determined that there is a protein in rat liver capable of inhibiting DNA polymerase alpha. To assay for this inhibitor, DNA polymerase alpha was purified from R3230AC rat mammary tumor, a rich source of this enzyme. Protein fractions from Sephacryl S200 gel filtration of total soluble liver extract showing inhibition of DNA polymerase alpha were further chromatographed on DEAE-cellulose. This step revealed two inhibitor protein populations with the major form corresponding to a molecular weight of 143,000 dalton. Soluble extract from isolated rat liver nuclei also showed the presence of at least two inhibitors; the major form was 200,000+ dalton in molecular weight. Both the 143,000 and 200,000+ dalton inhibitor proteins were capable of inhibiting the R3230AC tumor DNA polymerase alpha in a dose-dependent manner. These inhibitors exhibited similar inhibition of nuclear matrix-associated DNA polymerase alpha from either the R3230AC tumor or from regenerating rat liver.
D000818:Animals; D002850:Chromatography, Gel; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D008099:Liver / Q000032:analysis*; D008115:Liver Regeneration; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology; D008970:Molecular Weight; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004791:Enzyme Inhibitors; D011506:Proteins; D004257:DNA Polymerase II