CYTOSKELETAL INVOLVEMENT IN CAMP-INDUCED SENSITIZATION OF CHROMATIN TO NUCLEASE DIGESTION IN TRANSFORMED CHINESE-HAMSTER OVARY K1-CELLS

The cAMP-induced reverse transformation of CHO-K1 cells, which restores fibroblastic morphology, normal nuclear structure, specific membrane structures and biochemical activities and cell growth regulation, also restores the sensitivity of nuclear chromatin digestion by DNase I to that resembling the normal fibroblast. All of these aspects of the reverse-transformation reaction require integrity of the cytoskeleton. The nuclease-sensitivity effect is achieved only when the entire cell rather than the isolated nucleus is incubated with cAMP derivatives, indicating linkage between the cytoskeleton and nuclear components. Evidence is presented to show that the DNA sensitization to digestion involves interaction between DNA and other chromatin components and affects different regions of the genome is specific ways. Normal fibroblasts display greater endogenous nuclease activity than the transformed cell. The data are interpreted in terms of a genetic regulatory system extending from the membrane to the nucleus and utilizing the cAMP-induced cytoskeleton.