Regulation of the synthesis of DNA polymerase-alpha in regenerating liver by calcium and 1,25-dihydroxyvitamin D3.

Digestion of nuclei from normal or partially hepatectomised rat livers with endogenous nucleases liberated a pool of cryptic DNA polymerase-alpha activity which had previously gone unrecognised. Most of this activity is released into the supernatant as free enzyme molecules (11S), but a small fraction of it is released as a complex of 16S (probably with DNA primase). About 40% of the enzyme remains in the pellet, which contains undigested chromatin and components of the residual nuclear matrix and nucleoskeletal structures. Virtually all of this remaining activity is extracted by 2.0 M salt. The activity of DNA polymerase-alpha increases equally in all nuclear fractions during the period of DNA replication in regenerating rat liver. Lowering of the serum calcium level by thyroparathyroidectomy does not affect basal DNA polymerase-alpha activity, but prevents induction of the enzyme during the later stages of prereplicative development. However, an injection of 1 alpha,25-dihydroxy vitamin D3 into the rat during the first 6 h after parital hepatectomy restores the ability of the hepatocytes to induce DNA polymerase-alpha activity and initiate DNA synthesis. These results are discussed in terms of the role of calcium ions in the regulation of the critical stage of prereplicative development which commits the cells to DNA replication.