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

Proc Natl Acad Sci U S A. 1981 Jun;78(6):3673-7. doi: 10.1073/pnas.78.6.3673.

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

  • Animals
  • Cell Cycle
  • Cell Line
  • Cocarcinogenesis
  • Gene Amplification*
  • Neoplasms / genetics*
  • Phenotype
  • Replicon*
  • Virus Replication