Hypothesis: Local variations in the speed of individual DNA replication forks determine the phenotype of daughter cells

Abstract : How a cell coordinates its thousands of different constituents to achieve coherent – but different – phenotypes is far from fully understood. It is clear though that daughter cells with different phenotypes can be generated by the cell cycle, which comprises the events of chromosome replication, chromosome segregation and cell division. In line with this, recent experiments are consistent with an intimate relationship in bacteria between the speed of chromosome replication at a fork(s) and metabolism. The process of chromosome replication progressively changes the copy number of genes and sites in a linear order. This raises the possibility that speeding up or slowing down or even pausing replication for different times at different sites in the chromosome might be combined with various mechanisms leading to local cooperation (for example, the transcription of a gene leading to more transcription of that gene) and to global competition (for example, a gene having to compete with all the other genes for the transcriptional apparatus). If so, such replication-phenotype coupling could produce different patterns of gene expression and metabolic activity. Indeed, replication-phenotype coupling may constitute a powerful and fundamental way of generating coherent phenotypes, that is, phenotypes in which the cell's constituents perform compatible functions (rather than, for example, trying to maintain growth and to shut down growth simultaneously). In this hypothesis, such coupling would involve the dynamics of the spatially extended assemblies of molecules and macromolecules termed 'hyperstructures'. As a prelude to testing this hypothesis, we discuss some of the parameters that will need to be explored by bench experimentation and computer simulation.
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Submitted on : Wednesday, December 27, 2017 - 5:32:31 PM
Last modification on : Thursday, October 10, 2019 - 11:40:05 AM

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Vic Norris, François Képès, Patrick Amar, Ina Koch, Laurent Janniere. Hypothesis: Local variations in the speed of individual DNA replication forks determine the phenotype of daughter cells. Medical Research Archives, KEI Journals, 2017, 5 (12), ⟨10.18103/mra.v5i12.1598⟩. ⟨hal-01672912⟩

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