Internal motion of supercoiled DNA: brownian dynamics simulations of site juxtaposition

Jian, Hongmei; Schlick, Tamar; Vologodskii, Alexander

doi:10.1006/jmbi.1998.2170

Cited by 96 publications

(112 citation statements)

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“…This value is significantly larger than that of the relaxed plasmid (P = 8.0×10 −3 ) and reflects the influence of the geometrical constraints on the plasmid compared with the linear tether. These findings support the idea, consistent with previously proposed models (19), that juxtaposition kinetics are dependent on supercoiling as the internal motion of a DNA molecule is accelerated when the DNA is supercoiled. This is important as the frequency of site juxtaposition, in this case operator site juxtaposition, is believed to be a key factor in the occurrence of DNA looping (16,18,28).…”

Section: Resultssupporting

confidence: 92%

“…Further, we found that the supercoiled plasmid exhibited a much faster relaxation time than the relaxed plasmid and the linear tether, which is analogous to enhanced site juxtaposition in the supercoiled state. These findings support previously published molecular dynamics simulations (19) and in vitro transcription assays (18).…”

Section: Discussionsupporting

confidence: 92%

“…In comparison, a relaxed DNA of the same size is less compact and bears a much smaller number of juxtaposed sites. Brownian dynamics simulations scrutinizing the thermal motion of relaxed and supercoiled DNA suggest a dynamic difference between the two (19). The simulations predicted that site juxtaposition is in general a slow process, which is accelerated by supercoiling.…”

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confidence: 99%

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DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch

Nørregaard

Andersson

Sneppen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Bacteriophage λ stably maintains its dormant prophage state but efficiently enters lytic development in response to DNA damage. The mediator of these processes is the λ repressor protein, CI, and its interactions with λ operator DNA. This λ switch is a model on the basis of which epigenetic switch regulation is understood. Using single molecule analysis, we directly examined the stability of the CI-operator structure in its natural, supercoiled state. We marked positions adjacent to the λ operators with peptide nucleic acids and monitored their movement by tethered particle tracking. Compared with relaxed DNA, the presence of supercoils greatly enhances juxtaposition probability. Also, the efficiency and cooperativity of the λ switch is significantly increased in the supercoiled system compared with a linear assay, increasing the Hill coefficient. The decision between the dormant state (the lysogenic state) and the vegetative state (the lytic state) made by bacteriophage λ upon infection of an Escherichia coli was the first epigenetic switch to be deciphered (1) and continues to provide insights into biological processes (2, 3). Once the lysogenic state is established, it is exceptionally stable and departure in the absence of the DNA damage sensing system is nearly always caused by mutation (4-6). Maintenance of lysogeny is mediated by the λ repressor protein, CI, and its formation of a complex with phage DNA. The CI protein binds at two regulatory regions called operator right (OR) and operator left (OL), located about 2.3 kbp apart on the phage genome. Each operator is a constellation of three adjacent subsites that each bind dimers of CI in a hierarchical manner (1, 7). In a lysogenic cell, CI prevents lytic growth by directly repressing the lytic promoters pR and pL. This repression is enhanced by longrange cooperative interactions between CI dimers bound to the OL1-OL2 and OR1-OR2 regions, thus looping the DNA that lies between them (8) (Fig. 1 A and B). CI-mediated DNA looping brings OR3 in proximity to OL3. This juxtaposition allows a CI dimer bound to the strong OL3 to facilitate another CI dimer to bind to the intrinsically weak OR3, thus reducing the concentration of CI necessary to occupy OR3. In this manner CI can autoregulate its own expression by binding to OR2 (activation) or by binding to OR3 (repression). This autoregulation is crucial for the phage to maintain repression while preventing excessive accumulation of CI. When DNA in the lysogen is damaged, the bacterial DNA-damage-sensing system is triggered, leading to CI inactivation by self-cleavage (9) and to an efficient switch to the lytic state, eventually leading to production of progeny phage and cell death (1).The switch from the lysogenic to the lytic state must be decisive. Partial entry into vegetative growth may kill the host without producing a full burst of progeny phage. Because the in vivo state of DNA is supercoiled (10), we sought to examine protein-mediated DNA looping on native, supercoiled DNA. In vitro single molecule exper...

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Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

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DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch

Nørregaard

Andersson

Sneppen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…11 As important as that work has been, the models employed in these references have not included excluded volume effects or hydrodynamic interactions, and therefore cannot be used as predictive tools for molecules of differing sizes. Furthermore, experimental evidence 3 indicates nonfree-draining behavior for DNA molecules as short as 3 m. Recent studies [12][13][14] have considered both excluded volume and hydrodynamic interactions in stochastic simulations of DNA. However, that work only considered chains of less than a micron in length and simulation times of less than a second.…”

Section: Introductionmentioning

confidence: 99%

Stochastic simulations of DNA in flow: Dynamics and the effects of hydrodynamic interactions

Jendrejack

Pablo

Graham

2002

The Journal of Chemical Physics

269

364

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We present a fully parametrized bead-spring chain model for stained -phage DNA. The model accounts for the finite extensibility of the molecule, excluded volume effects, and fluctuating hydrodynamic interactions ͑HI͒. Parameters are determined from equilibrium experimental data for 21 m stained -phage DNA, and are shown to quantitatively predict the non-equilibrium behavior of the molecule. The model is then used to predict the equilibrium and nonequilibrium behavior of DNA molecules up to 126 m. In particular, the HI model gives results that are in quantitative agreement with experimental diffusivity data over a wide range of molecular weights. When the bead friction coefficient is fit to the experimental relaxation time at a particular molecular weight, the stretch in shear and extensional flows is adequately predicted by either a free-draining or HI model at that molecular weight, although the fitted bead friction coefficients for the two models differ significantly. In shear flow, we find two regimes at high shear rate (␥ ) that follow different scaling behavior. In the first, the viscosity and first normal stress coefficient scale roughly as ␥ Ϫ6/11 and ␥ Ϫ14/11 , respectively. At higher shear rates, these become ␥ Ϫ2/3 and ␥ Ϫ4/3 . These regimes are found for both free-draining and HI models and can be understood based on scaling arguments for the diffusion of chain ends.

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“…aging investigations. (Nevertheless, it is justifiable to use static plasmid models in track structure calculations because the form of a plasmid molecule changes on a time scale of about 10 −6 s (Jian et al 1998) which is very slow compared to the duration of the chemical phase of the radiation action chain of about 10 −8 s.)…”

Section: Results and Conclusionmentioning

confidence: 99%

A computer-generated supercoiled model of the pUC19 plasmid

Kümmerle

Pomplun

2004

Eur Biophys J

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DNA models have become a powerful tool in the simulation of radiation-induced molecular damage. Here, a computer code was developed which calculates the coordinates of individual atoms in supercoiled plasmid DNA. In this prototype study, the known base pair sequence of the pUC19 plasmid has been utilised. The model was built in a three-step process. Firstly, a Monte Carlo simulation was performed to shape a segment chain skeleton. Checks on elastic energy, distance and unknotting were applied. The temperature was considered in two different ways: (a) it was kept constant at 293 K and (b) it was gradually reduced from 350 K to less than 10 K. Secondly, a special smoothing procedure was introduced here to remove the edges from the segment chain without changing the total curve length while avoiding the production of overshooting arcs. Finally, the base pair sequence was placed along the smoothed segment chain and the positions of all the atoms were calculated. As a first result, a few examples of the supercoiled plasmid models will be presented demonstrating the strong influence of appropriate control of the system temperature.

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Internal motion of supercoiled DNA: brownian dynamics simulations of site juxtaposition

Cited by 96 publications

References 50 publications

DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch

DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch

Stochastic simulations of DNA in flow: Dynamics and the effects of hydrodynamic interactions

A computer-generated supercoiled model of the pUC19 plasmid

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