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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

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

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

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

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

We propose a dynamical model for non-specific DNA-protein interaction, which is based on the 'bead-spring' model previously developed by other groups, and investigate its properties using Brownian Dynamics simulations. We show that the…

Biological Physics · Physics 2009-01-14 Ana-Maria Florescu , Marc Joyeux

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 a model for a protein searching for a target, using facilitated diffusion, on a DNA molecule confined in a finite volume. The model includes three distinct pathways for facilitated diffusion: (a) sliding - in which the protein…

Subcellular Processes · Quantitative Biology 2009-01-28 Michael Sheinman , Yariv Kafri

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

The mechanical model based on beads and springs, which we recently proposed to study non-specific DNA-protein interactions [J. Chem. Phys. 130, 015103 (2009)], was improved by describing proteins as sets of interconnected beads instead of…

Biological Physics · Physics 2009-10-29 Ana-Maria Florescu , Marc Joyeux

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

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

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

In bacteria, regulatory proteins search for a specific DNA binding target via "facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm, and 1D linear diffusion along the DNA contour. Using large scale Brownian dynamics…

Biological Physics · Physics 2013-09-05 C. A. Brackley , M. E. Cates , D. Marenduzzo

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

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

Several processes in the cell, such as gene regulation, start when key proteins recognise and bind to short DNA sequences. However, as these sequences can be hundreds of million times shorter than the genome, they are hard to find by simple…

Subcellular Processes · Quantitative Biology 2021-01-27 Markus Nyberg , Tobias Ambjörnsson , Per Stenberg , and Ludvig Lizana

Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the process of recognition, a protein rapidly searches for its specific site on a…

Biomolecules · Quantitative Biology 2007-05-23 Michael Slutsky , Leonid A. Mirny

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
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