Differential effects of heparin on replicative DNA synthesis and unscheduled DNA synthesis

The effect of heparin on DNA synthesis was compared between replicative DNA synthesis and unscheduled DNA synthesis. Replicative DNA synthesis in permeable cells or nuclei prepared from rapidly growing mouse ascites sarcoma cells was inhibited by heparin. Unscheduled DNA synthesis in nuclei isolated from normal rat liver or from mouse ascites sarcoma cells in stationary phase was stimulated by heparin at low concentrations but inhibited by high heparin concentrations. DNA polymerase activity assayed with activated calf thymus DNA and DNA polymerase alpha purified partially from mouse ascites sarcoma cells was inhibited with either calf thymus histones or heparin. DNA synthesis inhibited with histones was partially reactivated by heparin. Replicative DNA synthesis in permeable cells was inhibited by adding histones to the assay mixture, and the inhibited DNA synthesis was partially reactivated by low concentrations of heparin. These results indicated that the replicated sites (or replication machinery) in permeable cells or nuclei were largely unrestricted by histones and that heparin inhibition of replicative DNA synthesis was due to the direct inhibitory interaction of heparin with some essential component(s), such as DNA polymerase, of replication machinery.