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- Nilsson, Karin, et al.
(författare)
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A novel mechanism for activator-controlled initiation of DNA replication that resolves the auto-regulation sequestration paradox
- 2008
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Ingår i: ASPECTS OF PHYSICAL BIOLOGY: BIOLOGICAL WATER, PROTEIN SOLUTIONS, TRANSPORT AND REPLICATION. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783540787648 ; , s. 189-213
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Konferensbidrag (refereegranskat)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 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.
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| 2. |
- Swenson, Jan, 1966, et al.
(författare)
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Anomalous behaviour of supercooled water and its implication for protein dymamics
- 2008
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Ingår i: Lecture Notes in Physics; Aspects of Physical Biology: Biological water, Protein solutions,Transport and Replication. - Berlin : Springer-Verlag Berlin. - 9783540787648 ; , s. 23-42
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Water is the foundation of life, and without it life as we know it would not exist. An organism consists to a large extent of water and, apart from a few larger reservoirs, almost all water in a living organism is closely associated with surfaces of biomolecules of different kinds. This so-called biological water is known to affect the dynamics of biomaterials such as proteins, which. in turn is crucial for its functions. However, how and why the surrounding environment affects the dynamics of proteins and other biomolecules is still not fully understood. Recently, it was suggested [Fenimore et al. PNAS 2004, 101 14408] that local and more global protein motions are slaved (or driven) by the local beta-relaxation and the more large-scale cooperative a-relaxation in the surrounding solvent, respectively. In this chapter we present results from dielectric measurements on myoglobin in water-glycerol mixtures that support this slaving idea. Moreover, we show how confined supercooled water changes its dynamical behaviour from a low temperature Arrhenius behaviour to a high temperature non-Arrhenius behaviour at a certain temperature (around 200 K), and then we discuss likely explanations for the crossover and its consequence for protein dynamics.
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