Effect of DNA conformation on facilitated diffusion

2013 ◽  
Vol 41 (2) ◽  
pp. 582-588 ◽  
Author(s):  
Chris A. Brackley ◽  
Mike E. Cates ◽  
Davide Marenduzzo

Within a living cell, site-specific DNA-binding proteins need to search the whole genome to find a target of ~10–20 bp. That they find the target, and do so quickly, is vital for the correct functioning of the DNA, and of the cell as a whole. The current understanding is that this search is performed via facilitated diffusion, i.e. by combining three-dimensional bulk diffusion within the cytoplasm or nucleoplasm, with one-dimensional diffusion along the DNA backbone, to which the protein binds non-specifically. After reviewing the standard theory of facilitated diffusion, we discuss in the present article the still rather rare direct computer simulations of this process, focusing on the three-dimensional part of the search, and the effect of DNA looping and the general DNA conformation on its efficiency. We close by highlighting some open questions in this field.

2018 ◽  
Author(s):  
Iddo Heller ◽  
Margherita Marchetti ◽  
Abhishek Mazumder ◽  
Anirban Chakraborty ◽  
Agata M. Malinowska ◽  
...  

ABSTRACTThe search for a promoter on DNA by RNA polymerase (RNAP) is an obligatory first step in transcription. The role of facilitated diffusion during promoter search has been controversial. Here, we re-assessed facilitated diffusion in promoter search by imaging motions of single molecules of Escherichia coli RNAP σ70 holoenzyme on single DNA molecules suspended between optical traps in a manner that absolutely avoided interactions with surfaces. The assay enabled us to observe unambiguous one-dimensional sliding of RNAP σ70 holoenzyme for thousands of DNA base pairs during promoter search. Analysis of binding kinetics revealed short binding events on nonspecific DNA (0.4 s), intermediate binding events on A/T-rich DNA (1.6 s), and long binding events at or near promoters (>300 s). We estimate a lower bound for the “diffusion facilitation threshold” – the RNAP concentration at which three-dimensional search and one-dimensional sliding contribute equally to promoter binding – of 0.2 μM RNAP. The results suggest facilitated diffusion occurs in promoter search by RNAP, even at the relatively high, 0.2-0.6 μM, concentrations of RNAP in cells.Significance statementThe flow of genetic information from DNA to RNA is of central importance to living systems, and it can only start after an RNA polymerase (RNAP) has found a promoter site. But how does this enzyme find promoter sites on DNA in the first place? In recent years, debate on this topic has favored a promoter search mechanism that is dominated by three-dimensional diffusion of RNAP, rather than by one-dimensional sliding of RNAP on DNA. Here, we designed an improved single-molecule assay that unambiguously revealed extensive one-dimensional sliding of RNAP on DNA. Our results imply that, at the RNAP concentrations in living cells, the promoter-search process is facilitated by one-dimensional sliding on DNA.


Author(s):  
Peter Sterling

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.


2008 ◽  
Vol 67 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Stefano Passini

The relation between authoritarianism and social dominance orientation was analyzed, with authoritarianism measured using a three-dimensional scale. The implicit multidimensional structure (authoritarian submission, conventionalism, authoritarian aggression) of Altemeyer’s (1981, 1988) conceptualization of authoritarianism is inconsistent with its one-dimensional methodological operationalization. The dimensionality of authoritarianism was investigated using confirmatory factor analysis in a sample of 713 university students. As hypothesized, the three-factor model fit the data significantly better than the one-factor model. Regression analyses revealed that only authoritarian aggression was related to social dominance orientation. That is, only intolerance of deviance was related to high social dominance, whereas submissiveness was not.


2020 ◽  
Vol 2020 (9) ◽  
Author(s):  
Rodolfo Panerai ◽  
Antonio Pittelli ◽  
Konstantina Polydorou

Abstract We find a one-dimensional protected subsector of $$ \mathcal{N} $$ N = 4 matter theories on a general class of three-dimensional manifolds. By means of equivariant localization we identify a dual quantum mechanics computing BPS correlators of the original model in three dimensions. Specifically, applying the Atiyah-Bott-Berline-Vergne formula to the original action demonstrates that this localizes on a one-dimensional action with support on the fixed-point submanifold of suitable isometries. We first show that our approach reproduces previous results obtained on S3. Then, we apply it to the novel case of S2× S1 and show that the theory localizes on two noninteracting quantum mechanics with disjoint support. We prove that the BPS operators of such models are naturally associated with a noncom- mutative star product, while their correlation functions are essentially topological. Finally, we couple the three-dimensional theory to general $$ \mathcal{N} $$ N = (2, 2) surface defects and extend the localization computation to capture the full partition function and BPS correlators of the mixed-dimensional system.


2021 ◽  
Vol 22 (5) ◽  
pp. 2398
Author(s):  
Wooyoung Kang ◽  
Seungha Hwang ◽  
Jin Young Kang ◽  
Changwon Kang ◽  
Sungchul Hohng

Two different molecular mechanisms, sliding and hopping, are employed by DNA-binding proteins for their one-dimensional facilitated diffusion on nonspecific DNA regions until reaching their specific target sequences. While it has been controversial whether RNA polymerases (RNAPs) use one-dimensional diffusion in targeting their promoters for transcription initiation, two recent single-molecule studies discovered that post-terminational RNAPs use one-dimensional diffusion for their reinitiation on the same DNA molecules. Escherichia coli RNAP, after synthesizing and releasing product RNA at intrinsic termination, mostly remains bound on DNA and diffuses in both forward and backward directions for recycling, which facilitates reinitiation on nearby promoters. However, it has remained unsolved which mechanism of one-dimensional diffusion is employed by recycling RNAP between termination and reinitiation. Single-molecule fluorescence measurements in this study reveal that post-terminational RNAPs undergo hopping diffusion during recycling on DNA, as their one-dimensional diffusion coefficients increase with rising salt concentrations. We additionally find that reinitiation can occur on promoters positioned in sense and antisense orientations with comparable efficiencies, so reinitiation efficiency depends primarily on distance rather than direction of recycling diffusion. This additional finding confirms that orientation change or flipping of RNAP with respect to DNA efficiently occurs as expected from hopping diffusion.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiang Wang ◽  
Yong Ge ◽  
Hong-xiang Sun ◽  
Haoran Xue ◽  
Ding Jia ◽  
...  

AbstractCrystalline materials can host topological lattice defects that are robust against local deformations, and such defects can interact in interesting ways with the topological features of the underlying band structure. We design and implement a three dimensional acoustic Weyl metamaterial hosting robust modes bound to a one-dimensional topological lattice defect. The modes are related to topological features of the bulk bands, and carry nonzero orbital angular momentum locked to the direction of propagation. They span a range of axial wavenumbers defined by the projections of two bulk Weyl points to a one-dimensional subspace, in a manner analogous to the formation of Fermi arc surface states. We use acoustic experiments to probe their dispersion relation, orbital angular momentum locked waveguiding, and ability to emit acoustic vortices into free space. These results point to new possibilities for creating and exploiting topological modes in three-dimensional structures through the interplay between band topology in momentum space and topological lattice defects in real space.


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