The interaction of natural and synthetic polyanions with mammalian nuclei: I. DNA synthesis

Abstract

Isolated nuclei or soluble chromatin prepared from rat liver are incapable of serving in vitro as an effective template for the enzymatic synthesis of DNA with exogenous DNA polymerase. These template restrictions on nuclear DNA may be overcome by the presence of certain specific polyanions such as heparin, polyaspartic acid, and dextran sulfate. In contrast, similar types of polyanions such as chondroitin sulfate, casein, polygalacturonic acid, and hyaluronic acid are without effect. This marked specificity of certain polyanions for activating the template properties of nuclei and chromatin is not simply related to the ionic strength of the system but is a function of the molecular weight and charge distribution of the polyanion. Polyaspartic acid (20 000 mol. wt.) is a very effective activator of soluble chromatin, while the 5600 mol. wt. polymer is not effective. Some of these polyanions are potent inhibitors of DNA polymerase, thus producing a biphasic curve in the activation of the DNA template properties of nuclei and soluble chromatin.