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A novel mechanism for activator-controlled initiation of DNA replication that resolves the auto-regulation sequestration paradox
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology. (ehrenberg)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology. (ehrenberg)
2008 (English)In: ASPECTS OF PHYSICAL BIOLOGY: BIOLOGICAL WATER, PROTEIN SOLUTIONS, TRANSPORT AND REPLICATION / [ed] Franzese G, Rubi M, 2008, 189-213 p.Conference paper, Published paper (Refereed)
Abstract [en]

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 bacteriumEscherichia 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.

Place, publisher, year, edition, pages
2008. 189-213 p.
Series
Lecture Notes in Physics, ISSN 0075-8450 ; 752
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-104056DOI: 10.1007/978-3-540-78765-5_9ISI: 000258026700009ISBN: 978-3-540-78764-8 (print)OAI: oai:DiVA.org:uu-104056DiVA: diva2:219308
Conference
Conserence on Aspects of Physical Biology Sitges, SPAIN, JUN 05-09, 2006
Available from: 2009-05-27 Created: 2009-05-27 Last updated: 2011-04-21Bibliographically approved

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