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Proteins are known to locate their specific targets on DNA up to two orders of magnitude faster than predicted by the Smoluchowski three-dimensional diffusion rate. One of the mechanisms proposed to resolve this discrepancy is termed…

Biomolecules · Quantitative Biology 2011-11-10 Tao Hu , B. I. Shklovskii

The model of facilitated diffusion describes how DNA-binding proteins, such as transcription factors (TFs), find their chromosomal targets by combining 3D diffusion through the cytoplasm and 1D sliding along nonspecific DNA sequences. The…

Quantitative Methods · Quantitative Biology 2008-09-08 Gene-Wei Li , Otto G. Berg , Johan Elf

We study the impact of DNA coiling on the search rate of proteins moving along the DNA contour interspersed by three-dimensional (3D) bulk excursions. When the DNA is coiled proteins performing short 3D hops along a DNA segment can be…

Statistical Mechanics · Physics 2009-05-20 Michael A. Lomholt , Bram van den Broek , Svenja-Marei J. Kalisch , Gijs J. L. Wuite , Ralf Metzler

Some proteins can find their targets on DNA faster than by pure diffusion in the three-dimensional cytoplasm, through the process of facilitated diffusion: They can loosely bind to DNA and temporarily slide along it, thus being guided by…

Biomolecules · Quantitative Biology 2024-02-27 Michael A. Lomholt , Ralf Metzler

Strong experimental and theoretical evidence shows that transcription factors and other specific DNA-binding proteins find their sites using a two-mode search: alternating between 3D diffusion through the cell and 1D sliding along the DNA.…

Biomolecules · Quantitative Biology 2008-06-11 Zeba Wunderlich , Leonid A. Mirny

The diffusion-controlled limit of reaction times for site-specific DNA-binding proteins is derived from first principles. We follow the generally accepted concept that a protein propagates via two competitive modes, a three-dimensional…

Biological Physics · Physics 2009-11-11 Konstantin V. Klenin , Holger Merlitz , Joerg Langowski , Chen-Xu Wu

For most of the important processes in DNA metabolism, a protein has to reach a specific binding site on the DNA. The specific binding site may consist of just a few base pairs while the DNA is usually several millions of base pairs long.…

Statistical Mechanics · Physics 2010-01-10 Debanjan Chowdhury

It has long been asserted that proteins like transcription factors may locate their target in DNA sequences at rates that surpass by several orders of magnitude the three-dimensional diffusion limit thank to facilitated diffusion, that is…

Biological Physics · Physics 2010-09-27 Ana-Maria Florescu , Marc Joyeux

We study the target searching on the DNA for proteins in the presence of non-constant drift and non-Gaussian $\alpha$-stable L\'evy fluctuations. The target searching is realized by the facilitated diffusion process. The existing works are…

Statistical Mechanics · Physics 2019-03-27 Xi Chen , Xiujun Cheng , Yanmei Kang , Jinqiao Duan

In living cells, proteins combine 3D bulk diffusion and 1D sliding along the DNA to reach a target faster. This process is known as facilitated diffusion, and we investigate its dynamics in the physiologically relevant case of confined DNA.…

Soft Condensed Matter · Physics 2015-06-12 G. Foffano , D. Marenduzzo , E. Orlandini

We present a theoretical model of facilitated diffusion of proteins in the cell nucleus. This model, which takes into account the successive binding/unbinding events of proteins to DNA, relies on a fractal description of the chromatin which…

Statistical Mechanics · Physics 2015-05-19 O. Benichou , C. Chevalier , B. Meyer , R. Voituriez

We present Brownian dynamics simulations of the facilitated diffusion of a protein, modelled as a sphere with a binding site on its surface, along DNA, modelled as a semi-flexible polymer. We consider both the effect of DNA organisation in…

Biological Physics · Physics 2012-12-10 C. A. Brackley , M. E. Cates , D. Marenduzzo

Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and…

Subcellular Processes · Quantitative Biology 2015-06-12 Max Bauer , Ralf Metzler

In gene expression, various kinds of proteins need to bind to specific locus of DNA. It is still not clear how these proteins find their target locus. In this study, the mean first-passage time (FPT) of protein binding to its target locus…

Biological Physics · Physics 2016-06-20 Jingwei Li , Yunxin Zhang

Protein complexes involved in DNA mismatch repair appear to diffuse along dsDNA in order to locate a hemimethylated incision site via a dissociative mechanism. Here, we study the probability that these complexes locate a given target site…

Subcellular Processes · Quantitative Biology 2021-05-12 Kyle Crocker , James London , Andrés Medina , Richard Fishel , Ralf Bundschuh

We study a protein-DNA target search model with explicit DNA dynamics applicable to in vitro experiments. We show that the DNA dynamics plays a crucial role for the effectiveness of protein "jumps" between sites distant along the DNA…

Biomolecules · Quantitative Biology 2015-05-30 Thomas Schötz , Richard A. Neher , Ulrich Gerland

Cellular responses often require the fast activation or repression of specific genes, which depends on Transcription Factors (TFs) that have to quickly find the promoters of these genes within a large genome. Transcription Factors (TFs)…

Subcellular Processes · Quantitative Biology 2015-09-02 Jérôme Cartailler , Jürgen Reingruber

Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events…

Quantitative Methods · Quantitative Biology 2015-07-10 Maximilian Bauer , Emil S. Rasmussen , Michael A. Lomholt , Ralf Metzler

Motivated by recent single molecule studies of proteins sliding on a DNA molecule, we explore the targeting dynamics of N particles ("proteins") sliding diffusively along a line ("DNA") in search of their target site (specific target…

Statistical Mechanics · Physics 2009-11-11 Igor M. Sokolov , Ralf Metzler , Kiran Pant , Mark C. Williams

The precision of biochemical signaling is limited by randomness in the diffusive arrival of molecules at their targets. For proteins binding to the specific sites on the DNA and regulating transcription, the ability of the proteins to…

Molecular Networks · Quantitative Biology 2013-08-01 Gasper Tkacik , William Bialek
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