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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Jun;78(6):3673–3677. doi: 10.1073/pnas.78.6.3673

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

A Varshavsky
PMCID: PMC319633  PMID: 6943571

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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