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

Varshavsky, Alexander (1981) On the possibility of metabolic control of replicon "misfiring": Relationship to emergence of malignant phenotypes in mammalian cell lineages. Proceedings of the National Academy of Sciences of the United States of America, 78 (6). pp. 3673-3677. ISSN 0027-8424. PMCID PMC319633. doi:10.1073/pnas.78.6.3673.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 1981 by the National Academy of Sciences. Communicated by Howard Green, March 11, 1981. I thank OlofSundin, James Barsoum, and Frederick Boyce for helpful discussions. I am particularly indebted to Howard Green for many useful comments on the early draft of the paper. Secretarial assistance by Nancy Fritz is gratefully acknowledged. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.
Subject Keywords:extrachromosomal nuclear DNA; double minute chromosomes; firones; tumor promoters
Issue or Number:6
PubMed Central ID:PMC319633
Record Number:CaltechAUTHORS:VARpnas81
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1601
Deposited By: Tony Diaz
Deposited On:02 Feb 2006
Last Modified:08 Nov 2021 19:11

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