Dynamical model of DNA-protein interaction: Effect of protein charge distribution and mechanical properties

Florescu, Ana-Maria; Joyeux, Marc

doi:10.1063/1.3216104

Cited by 28 publications

(52 citation statements)

References 58 publications

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“…is the electric charge that in previous work [47,48,49,50,51] was placed at the centre of each DNA bead, according to [116]. In equation (2) nm.…”

Section: -Conclusion and Outlookmentioning

confidence: 99%

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Compaction of bacterial genomic DNA: clarifying the concepts

Joyeux

2015

J. Phys.: Condens. Matter

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: The unconstrained genomic DNA of bacteria forms a coil, which volume exceeds 1000 times the volume of the cell. Since prokaryotes lack a membrane-bound nucleus, in sharp contrast with eukaryotes, the DNA may consequently be expected to occupy the whole available volume when constrained to fit in the cell. Still, it has been known for more than half a century that the DNA is localized in a well defined region of the cell, called the nucleoid, which occupies only 15% to 25% of the total volume. Although this problem has focused the attention of many scientists for the past decades, there is still no certainty concerning the mechanism that enables such a dramatic compaction. The goal of this Topical Review is to take stock of our knowledge on this question by listing all possible compaction mechanisms with the proclaimed desire to clarify the physical principles they are based upon and discuss them in the light of experimental results and the results of simulations based on coarse-grained models. In particular, the fundamental differences between ψ-condensation and segregative phase separation and between the condensation by small and long polycations are highlighted. This review suggests that the importance of certain mechanisms, like supercoiling and the architectural properties of DNA-bridging and DNA-bending nucleoid proteins, may have been overestimated, whereas other mechanisms, like segregative phase separation and the self-association of nucleoid proteins, as well as the possible role of the synergy of two or more mechanisms, may conversely deserve more attention.Keywords : bacteria, genomic DNA, nucleoid, compaction, coarse-grained model 2 -IntroductionIllustrations of the hierarchical compaction of genomic DNA in the nuclei of eukaryotic cells can be found in any textbook, from the initial wrapping of DNA around histone proteins to the final X-shaped chromosomes, through the various levels of fiber condensation. While seemingly simpler, the compaction of bacterial genomic DNA is nevertheless more poorly understood. One of the main reasons is that typical cell dimensions and DNA size of prokaryotes are significantly smaller than those of eukaryotes, with cell radii of the order of 1 µm against 10 to 100 µm and DNA size of the order of millions of base pairs against billions of base pairs. As a consequence, optical microscopy experiments are able to show that DNA occupies only a small part of the cell (from 15% to 25%) but fail to provide more detail because of resolution issues [1]. In contrast, electronic microscopy is able to provide information on the ultra-structure of the nucleoid (the region where the DNA is localized) but results depend dramatically on the experimental procedure that is used to prepare the cells [1,2]. Finally, the more recent techniques that consist in labeling specific genes with fluorescent dyes or proteins [3] usually provide information on the dynamics close to the loci of these genes but not on the global organization of the nucleoid. Owing to these difficulties, ev...

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“…is the electric charge that in previous work [47,48,49,50,51] was placed at the centre of each DNA bead, according to [116]. In equation (2) nm.…”

Section: -Conclusion and Outlookmentioning

confidence: 99%

“…As in previous work [46,47,48,49,50,51], each bead represents 15 DNA base pairs, has a hydrodynamic radius 78 . 1 = a nm, and is separated at equilibrium from the neighboring ones by a distance 0 .…”

mentioning

confidence: 99%

Compaction of bacterial genomic DNA: clarifying the concepts

Joyeux

2015

J. Phys.: Condens. Matter

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“…This also gives a rational basis to some ad-hoc protein sizes that had to be put by hand in recent coarse grained simulations of protein sliding on DNA to ensure the protein would not go closer to DNA than the distance observed in the non-specific complex [81,82,83].…”

Section: A Facilitated Slidingmentioning

confidence: 99%

Protein–DNA Electrostatics

Barbi¹,

Paillusson²

2013

Dynamics of Proteins and Nucleic Acids

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Gene expression and regulation rely on an apparently finely tuned set of reactions between some proteins and DNA. Such DNA-binding proteins have to find specific sequences on very long DNA molecules and they mostly do so in absence of any active process. It has been rapidly recognized that to achieve this task these proteins should be efficient at both searching (i.e. sampling fast relevant parts of DNA) and finding (i.e. recognizing the specific site).A two-mode search and variants of it have been suggested since the 70s to explain either a fast search or an efficient recognition. Combining these two properties at a phenomenological level is however more difficult as they appear to have antagonist roles. To overcome this difficulty, one may simply need to drop the dichotomic view inherent to the two-mode search and look more thoroughly at the set of interactions between DNA-binding proteins and a given 1 arXiv:1311.7496v1 [physics.bio-ph] 29 Nov 2013 DNA segment either specific or non-specific. This chapter demonstrates that, in doing so in a very generic way, one may indeed find a potential reconciliation between a fast search and an efficient recognition. Although a lot remains to be done, this could be the time for a change of paradigm.

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“…Consequently, 3D motion interspersed by 1D events comprises the most effective search strategy in terms of search-time minimization. This view, albeit with modifications, has been accepted by several groups and further elaborated [7][8][9][10][11][12].…”

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confidence: 99%

Physical aspects of precision in genetic regulation

2010

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The process by which transcription factors (TFs) locate specific DNA binding sites is stochastic and as such, is subject to a considerable level of noise. TFs diffuse in the three-dimensional nuclear space, but can also slide along the DNA. It was proposed that this sliding facilitates the TF molecules arriving to their binding site, by effectively reducing the dimensionality of diffusion. However, the possible implications of DNA sliding on the accuracy by which the nuclear concentration of TFs can be estimated were not examined. Here, we calculate the mean and the variance of the number of TFs that bind to their binding site in reduced and partially reduced diffusion dimensionality regimes. We find that a search process which combines three-dimensional diffusion in the nucleus with one-dimensional sliding along the DNA can reduce the noise in TF binding and in this way enables a better estimation of the TF concentration inside the nucleus.

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Dynamical model of DNA-protein interaction: Effect of protein charge distribution and mechanical properties

Cited by 28 publications

References 58 publications

Compaction of bacterial genomic DNA: clarifying the concepts

Compaction of bacterial genomic DNA: clarifying the concepts

Protein–DNA Electrostatics

Physical aspects of precision in genetic regulation

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