Facilitated diffusion with DNA coiling. 2009

Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
Department of Physics and Chemistry, MEMPHYS Center for Biomembrane Physics, University of Southern Denmark, Odense M, Denmark.

When DNA-binding proteins search for their specific binding site on a DNA molecule they alternate between linear 1-dimensional diffusion along the DNA molecule, mediated by nonspecific binding, and 3-dimensional volume excursion events between successive dissociation from and rebinding to DNA. If the DNA molecule is kept in a straight configuration, for instance, by optical tweezers, these 3-dimensional excursions may be divided into long volume excursions and short hops along the DNA. These short hops correspond to immediate rebindings after dissociation such that a rebinding event to the DNA occurs at a site that is close to the site of the preceding dissociation. When the DNA molecule is allowed to coil up, immediate rebinding may also lead to so-called intersegmental jumps, i.e., immediate rebindings to a DNA segment that is far away from the unbinding site when measured in the chemical distance along the DNA, but close by in the embedding 3-dimensional space. This effect is made possible by DNA looping. The significance of intersegmental jumps was recently demonstrated in a single DNA optical tweezers setup. Here we present a theoretical approach in which we explicitly take the effect of DNA coiling into account. By including the spatial correlations of the short hops we demonstrate how the facilitated diffusion model can be extended to account for intersegmental jumping at varying DNA densities. It is also shown that our approach provides a quantitative interpretation of the experimentally measured enhancement of the target location by DNA-binding proteins.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D004058 Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT. Diffusions
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins

Related Publications

Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
February 2012, Physical review. E, Statistical, nonlinear, and soft matter physics,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
January 2006, Physical review letters,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
April 2013, Biochemical Society transactions,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
January 2015, Biochemistry,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
July 2015, Physical review. E, Statistical, nonlinear, and soft matter physics,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
December 1986, The EMBO journal,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
January 1985, Journal of mathematical biology,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
April 2015, Nucleic acids research,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
October 2012, Physical review letters,
Michael A Lomholt, and Bram van den Broek, and Svenja-Marei J Kalisch, and Gijs J L Wuite, and Ralf Metzler
July 2006, The Journal of chemical physics,
Copied contents to your clipboard!