ROLE OF THE CYTOSKELETON IN GENOME REGULATION AND CANCER

This chapter discusses the role of cytoskeleton in genome regulation and cancer. It describes two-tiered theory of regulation of the mammalian genome to the problem of cancer. Cancer represents a distortion of normal metabolic regulation. Cancer cells exhibit a loss of differentiation properties and a concomitant loss of growth control. The phenomenon of reverse transformation offers a unique opportunity to study the molecular nature of cancer. The cancer cells revert to the normal phenotype in the presence of cell-specific agonists and return to their original malignant behavior on its removal. The two-tiered scheme for the regulation of the mammalian genome accounts for the mode of action of genes that are differentiation specific in the mammalian organism. The first step in the activation of such tissue-specific genes is their conversion from the sequestered to the exposed state. This involves transfer of the appropriate DNA from the interior of the nucleus to the region of the nuclear periphery and the necessary conformational changes and specific protein interactions that render such DNA susceptible to hydrolysis by DNase I. The second step, which resembles the corresponding process in bacteria, is activation or inactivation of the exposed genes as a result of interaction with appropriate effector molecules in the surrounding medium. The restoration of cytoskeletal control of nuclear function in reverse transformation allows increased genome exposure and access of DNA to specific transcriptional regulators. © 1992 Academic Press Inc.