title: 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 either intra- or extracellular origin. The term " "firone" is proposed for such a substance. It is shown that existence of firones could greatly speed up evolution of cellular systems under selection pressure, a developing tumor being one example of such a system. Experimentally testable predictions of the firone hypothesis are discussed.
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D003043:Cocarcinogenesis; D005784:Gene Amplification; D009369:Neoplasms / Q000235:genetics*; D010641:Phenotype; D012093:Replicon; D014779:Virus Replication