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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

The diffusive arrival of transcription factors at the promoter sites on the DNA sets a lower bound on how accurately a cell can regulate its protein levels. Using results from the literature on diffusion-influenced reactions, we derive an…

Molecular Networks · Quantitative Biology 2014-10-24 Joris Paijmans , Pieter Rein ten Wolde

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

Transcription regulation is largely governed by the profile and the dynamics of transcription factors' binding to DNA. Stochastic effects are intrinsic to this dynamics and the binding to functional sites must be controled with a certain…

Genomics · Quantitative Biology 2007-05-23 Erik Aurell , Aymeric Fouquier d'Herouel , Claes Malmnas , Massimo Vergassola

Transcription factors perform facilitated diffusion (3D diffusion in the cytosol and 1D diffusion on the DNA) when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on…

Molecular Networks · Quantitative Biology 2014-09-04 Armin P. Schoech , Nicolae Radu Zabet

Proteins can locate their specific targets on DNA up to two orders of magnitude faster than the Smoluchowski three-dimensional diffusion rate. This happens due to non-specific adsorption of proteins to DNA and subsequent one-dimensional…

Soft Condensed Matter · Physics 2007-05-23 Tao Hu , B. I. Shklovskii

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

Many transcription factors bind to DNA with a remarkable lack of specificity, so that regulatory binding sites compete with an enormous number of non-regulatory 'decoy' sites. For an auto-regulated gene, we show decoy sites decrease noise…

Molecular Networks · Quantitative Biology 2015-06-05 Anat Burger , Aleksandra M. Walczak , Peter G. Wolynes

We develop revised theoretical ideas on the mechanism by which the transcription factor proteins locate their specific binding sites on DNA faster than the three-dimensional (3D) diffusion controlled rate limit. We demonstrate that the…

Biological Physics · Physics 2014-09-22 Rajamanickam Murugan

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

We study by simulation the effect of the diffusive motion of repressor molecules on the noise in mRNA and protein levels in the case of a repressed gene. We find that spatial fluctuations due to diffusion can drastically enhance the noise…

Molecular Networks · Quantitative Biology 2007-05-23 Jeroen S. van Zon , Marco J. Morelli , Sorin Tanase-Nicola , Pieter Rein ten Wolde

It is known since the early days of molecular biology that proteins locate their specific targets on DNA up to two orders of magnitude faster than the Smoluchowski 3D diffusion rate. It was the idea due to Delbruck that they are…

Biomolecules · Quantitative Biology 2015-06-26 Tao Hu , A. Yu. Grosberg , B. I. Shklovskii

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

Transcription factor (TF) molecules translocate by facilitated diffusion (a combination of 3D diffusion around and 1D random walk on the DNA). Despite the attention this mechanism received in the last 40 years, only a few studies…

Subcellular Processes · Quantitative Biology 2013-09-20 Nicolae Radu Zabet , Boris Adryan

There is now a certain consensus that Transcription Factors (TFs) reach their target sites, where they regulate gene transcription, via a mechanism dubbed facilitated diffusion (FD). In FD, the TF cycles between events of 3D-diffusion in…

Biomolecules · Quantitative Biology 2015-06-18 Carlo Guardiani , Massimo Cencini , Fabio Cecconi

A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these…

Molecular Networks · Quantitative Biology 2016-02-10 Thomas R. Sokolowski , Aleksandra M. Walczak , William Bialek , Gašper Tkačik

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

In the course of various biological processes, specific DNA-binding proteins must find a particular target sequence/protein or a damaged site on the DNA efficiently. DNA-binding proteins perform this task based on diffusion. Yet,…

Biological Physics · Physics 2021-02-24 Seongyu Park , O-chul Lee , Xavier Durang , Jae-Hyung Jeon

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

We derive exact solutions of simplified models for the temporal evolution of the protein concentration within a cell population arbitrarily far from the stationary state. We show that monitoring the dynamics can assist in modeling and…

Biomolecules · Quantitative Biology 2015-05-13 Sandro Azaele , Jayanth R. Banavar , Amos Maritan
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