On the possibility of metabolic control of replicon "misfiring": relationship to emergence of malignant phenotypes in mammalian cell lineages.

Abstract

Constraints of a multireplicon chromosomal organization and of the necessity to maintain constant gene dosages demand that each origin of replication in a eukaryotic cell fire (initiate replication) only once per cell cycle. The central idea of this work is that a low probability of an extra (illegitimate) round of DNA replication (called below replicon misfiring) within any given chromosomal domain could be increased by certain substances of intra- or extracellular origin. The term firone is proposed for such a substance. Existence of firones could greatly speed up evolution of cellular systems under selection pressure, a developing tumor being one such a system. Experimentally testable predictions of the firone hypothesis are discussed.