DNA polymerase activities during erythropoiesis: Effects of erythropoietin, vinblastine, colcemid, and daunomycin

Abstract

Erythropoietin stimulates DNA synthesis in the spleen of the polycythemic mouse with the maximum effect occurring approx 48 h after the hormone is administered. The increase in DNA synthesis is accompanied by morphologic evidence of increased erythropoiesis, increased 59Fe incorporation into heme, and an increase in the activity of the cytoplasmic high molecular weight DNA polymerase (DNA polymerase-α). In contrast, the activity of the low molecular weight DNA polymerase (DNA polymerase-β) does not significantly change after administration of erythropoietin. Vinblastine, colcemid, and daunomycin prevent the effects of erythropoietin on mouse spleen, so that increases in DNA synthesis, DNA polymerase-α, and 59Fe incorporation do not occur. DNA polymerase-α may have a short half-life in cells since its activity is barely detectable 12 to 24 h after administration of inhibitors of cellular proliferation or nucleic acid synthesis. The half-life of DNA polymerase-β may be long since it is unaffected by these inhibitors. Cytoplasmic rather than nuclear DNA polymerases appear to play a major role in erythropoietin-stimulated DNA synthesis and replication of erythroid cells.