Abstract
For bacterial genes to be inherited to the next bacterial generation, the gene containing DNA sequences must be duplicated before cell division so that each daughter cell contains a complete set of genes. The duplication process is called DNA replication and it starts at one defined site on the DNA molecule called the origin of replication (oriC) [1]. In addition to chromosomal DNA, bacteria often also contain plasmid DNA. Plasmids are extra-chromosomal DNA molecules carrying genes that increase the fitness of their host in certain environments, with genes encoding antibiotic resistance as a notorious example [2]. The chromosome is found at a low per cell copy number and initiation of replication takes place synchronously once every cell generation [3,4], while many plasmids exist at a high copy number and replication initiates asynchronously, throughout the cell generation [5]. In this chapter we present a novel mechanism for the control of initiation of replication, where one type of molecule may activate a round of replication by binding to the origin of replication and also regulate its own synthesis accurately. This mechanism of regulating the initiation of replication also offers a novel solution to the so-called auto-regulation sequestration paradox, i.e. how a molecule sequestered by binding to DNA may at the same time accurately regulate its own synthesis [6]. The novel regulatory mechanism is inspired by the molecular set-up of the replication control of the chromosome in the bacterium Escherichia coli and is here transferred into a plasmid model. This allows us to illustrate principles of replication control in a simple way and to put the novel mechanism into the context of a previous analysis of plasmids regulated by inhibitor-dilution copy number control [7]. We analyze factors important for a sensitive response of the replication initiation rate to changes in plasmid concentration in an asynchronous model and discover a novel mechanism for creating a high sensitivity. We further relate sensitivity to initiation synchrony in a synchronous model. Finally, we discuss the relevance of these findings for the control of chromosomal replication in bacteria.
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Nilsson, K., Ehrenberg, M. (2009). A Novel Mechanism for Activator-Controlled Initiation of DNA Replication that Resolves the Auto-regulation Sequestration Paradox. In: Franzese, G., Rubi, M. (eds) Aspects of Physical Biology. Lecture Notes in Physics, vol 752. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78765-5_9
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DOI: https://doi.org/10.1007/978-3-540-78765-5_9
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