Multiple Aspects of DNA and RNA : Lecture Notes of the Les Houches Summer School 2004.
Title:
Multiple Aspects of DNA and RNA : Lecture Notes of the Les Houches Summer School 2004.
Author:
Chatenay, Didier.
ISBN:
9780080461540
Personal Author:
Edition:
1st ed.
Physical Description:
1 online resource (379 pages)
Series:
Les Houches ; v.82
Les Houches
Contents:
Previous sessions -- Lecturers -- Short lectures and seminar speakers -- Organizers -- Participants -- Preface -- Contents -- DNA structure, dynamics and recognition -- Introduction to the DNA double helix -- Biophysical studies of DNA - structure and stability -- DNA dynamics -- Deformations of the double helix -- DNA recognition -- Introduction to non-Watson-Crick base pairs and RNA folding -- Definitions -- The annotation of non-Watson-Crick base pairs and of RNA motifs -- RNA-RNA recognition motifs -- Roles of RNA motifs in RNA-protein recognition -- Conclusions -- References -- Regulation of transcription by RNA polymerase II -- Introduction -- DNA regulatory elements -- Basal/general transcription factors -- Sequence-specific DNA-binding factors -- Chromatin and transcription -- Conclusions and speculations -- References -- Basic concepts of statistical physics of polymers -- Introduction to polymer physics -- Fundamentals of physical viewpoint in polymer science -- Flexibility of a polymer chain. Flexibility mechanisms -- Rotational-isomeric flexibility mechanism -- Persistent flexibility mechanism -- Freely-jointed flexibility mechanism -- Types of polymer molecules -- Physical states of polymer materials -- Polymer solutions -- Single ideal polymer chain -- Definition of ideal polymer chain -- Size of ideal freely-jointed chain. Entangled coil -- Size of ideal chain with fixed valency angle -- Kuhn segment length of a polymer chain -- Persistent length of a polymer chain -- Stiff and flexible chains -- Gaussian distribution for the end-to-end vector for ideal chain -- High elasticity of polymer networks -- The property of high elasticity -- Elasticity of a single ideal chain -- Elasticity of a polymer network (rubber) -- Viscoelasticity of entangled polymer fluids -- Main properties of entangled polymer fluids -- Viscosity of fluids.
The property of viscoelasticity -- Theory of reptations -- The method of gel-electrophoresis in application to DNA molecules -- Gel permeation chromatography -- References -- The physics of DNA electrophoresis -- Importance of DNA sorting in biology and how physics can help -- Physical description of DNA -- Electrophoretic force -- DNA sequencing: gel electrophoresis of single-stranded DNA -- Reptative dynamics -- Biased reptation -- Repton model -- Strategies for DNA sequencing -- Gel electrophoresis of long double-stranded DNA molecules -- Complex dynamics in constant fields -- Pulsed-field gel electrophoresis: separation of restriction fragments -- Difficulty of separating very large molecules -- Obstacle courses on microchips -- Collision of a DNA molecule with an obstacle -- Efficient pulsed-field fractionation in silicon arrays -- Continuous separation in asymmetric pulsed fields -- Asymmetric sieves for sorting DNA -- Rapid continuous separation in a divided laminar flow -- Summary -- References -- Single-molecule studies of DNA mechanics and DNA/protein interactions -- Introduction -- The interest of physicists for DNA -- Ease of handling -- DNA as a model polymer -- Introduction to single-molecule DNA manipulation techniques -- Strategies and forces involved -- Measurement techniques -- Force measurements -- Measuring forces with Brownian motion -- Advantages and disadvantages of the manipulation techniques -- Mechanical properties and behavior of DNA -- Tertiary structures in DNA -- Topological formalism -- DNA supercoiling in vivo -- DNA unwinding and helix destabilisation -- DNA topoisomerases -- Supercoiling and transcription -- DNA elasticity in the absence of torsion (sigma=0) -- Results -- Theoretical models -- Mechanical properties of supercoiled DNA -- Results -- Interpretation -- The buckling instability in DNA.
Stretching single-strand DNA -- Conclusions on the mechanical properties of nucleic acids -- RNA polymerases -- An introduction to transcription -- Historical overview: transcription elongation, or RNA polymerase as a linear motor -- RNA polymerase as a torquing device: the case of transcription initiation -- DNA topoisomerases -- Type I and Type II topoisomerases -- Eukaryotic topoisomerase II -- Enzymatic cycle -- Prokaryotic topoisomerase IV -- Experimental results: D. melanogaster topoisomerase II -- Calibrating the experiment -- Crossover clamping in the absence of ATP -- Low ATP concentrations: detecting a single enzymatic cycle -- High ATP concentration -- Determining Vsat, the saturated reaction velocity -- Effect of the stretching force -- Relaxation of negatively supercoiled DNA -- Topo II only removes crossovers in DNA -- A comparison with E. coli topo IV -- Experiments on braided DNA molecules -- Conclusions on type II topoisomerases -- Conclusions and future prospects -- References -- Introduction to single-DNA micromechanics -- Introduction -- The double helix is a semiflexible polymer -- Structure -- DNA bending -- Discrete-segment model of a semiflexible polymer -- Bending elasticity and the persistence length -- End-to-end distance -- DNA loop bending energies -- Site-juxtaposition probabilities -- Permanent sequence-driven bends -- Stretching out the double helix -- Small forces ( kB T/A = 0.08 pN) -- Free energy of the semiflexible polymer -- Really large forces (> 10 pN) -- Strand separation -- Free-energy models of strand separation -- Sequence-dependent models -- Free energy of internal `bubbles' -- Small internal bubbles may facilitate sharp bending -- Stretching single-stranded nucleic acids -- Unzipping the double helix -- Effect of torque on dsDNA end.
Fixed extension versus fixed force for unzipping -- DNA topology -- DNA supercoiling -- Twist rigidity of the double helix -- Writhing of the double helix -- Simple model of plectonemic supercoiling -- Twisted DNA under tension -- Forces and torques can drive large structural reorganizations of the double helix -- DNA knotting -- Cells contain active machinery for removal of knots and other entanglements of DNA -- Knotting a molecule is surprisingly unlikely -- Condensation-resolution mechanism for disentangling long molecules -- DNA-protein interactions -- How do sequence-specific DNA-binding proteins find their targets? -- Three-dimensional diffusion to the target -- Nonspecific interactions can accelerate targeting -- Single-molecule study of DNA-binding proteins -- DNA-looping protein: equilibrium `length-loss' model -- Loop formation kinetics -- DNA-bending proteins -- Analytical calculation for compaction by DNA-bending proteins -- Effects of twisting of DNA by proteins -- Surprising results of experiments -- Conclusion -- References -- The analysis of regulatory sequences -- Forewords -- Scope of the course -- Web site and practical sessions -- Transcriptional regulation -- The non-coding genome -- Transcriptional regulation -- Representations of regulatory elements -- String-based representations -- Matrix-based representation -- Pattern discovery -- Introduction -- Study cases -- String-based pattern discovery -- Analysis of word occurrences -- Analysis of dyad occurrences (spaced pairs of words) -- Strengths and weaknesses of word- and dyad-based pattern discovery -- String-based pattern matching -- Matrix-based pattern discovery -- Consensus: a greedy approach -- Gibbs sampling -- Strengths and weaknesses of matrix-based pattern discovery -- Concluding remarks -- Practical sessions -- Appendices -- IUPAC ambiguous nucleotide code.
A survey of gene circuit approach applied to modelling of segment determination in fruitfly -- Preamble -- Introduction -- The biology of segment determination -- Method description -- The gene circuit modelling framework -- Quantitative expression data -- Optimization by Parallel Lam Simulated Annealing (PLSA) and Optimal Steepest Descent Algorithm (OSDA) -- Selection of gene circuits -- Software and bioinformatics -- Analysis of regulatory mechanisms controlling segment determination -- Regulatory interactions in gap gene system -- Stripe forming architecture of the gap gene system -- Pattern formation and nuclear divisions are uncoupled in Drosophila segmentation -- Conclusions -- References -- Modeling, analysis, and simulation of genetic regulatory networks: from differential equations to logical models -- Introduction -- Ordinary differential equations -- Models and analysis -- Analysis of regulatory networks involved in cell-cycle control, circadian rhythms, and development -- Piecewise-linear differential equations -- Models and analysis -- Simulation of the initiation of sporulation in Bacillus subtilis -- Logical models -- Models and analysis -- Modeling of the lysis-lysogeny decision during the infection of Escherichia coli by bacteriophage lambda -- Extensions of logical modeling -- Conclusions -- References.
Abstract:
This book is dedicated to the multiple aspects, that is, biological, physical and computational of DNA and RNA molecules. These molecules, central to vital processes, have been experimentally studied by molecular biologists for five decades since the discovery of the structure of DNA by Watson and Crick in 1953. Recent progresses (e.g. use of DNA chips, manipulations at the single molecule level, availability of huge genomic databases...) have revealed an imperious need for theoretical modelling. Further progresses will clearly not be possible without an integrated understanding of all DNA and RNA aspects and studies. The book is intended to be a desktop reference for advanced graduate students or young researchers willing to acquire a broad interdisciplinary understanding of the multiple aspects of DNA and RNA. It is divided in three main sections: The first section comprises an introduction to biochemistry and biology of nucleic acids. The structure and function of DNA are reviewed in R. Lavery's chapter. The next contribution, by V. Fritsch and E. Westhof, concentrates on the folding properties of RNA molecules. The cellular processes involving these molecules are reviewed by J. Kadonaga, with special emphasis on the regulation of transcription. These chapters does not require any preliminary knowledge in the field (except that of elementary biology and chemistry). The second section covers the biophysics of DNA and RNA, starting with basics in polymer physics in the contribution by R. Khokhlov. A large space is then devoted to the presentation of recent experimental and theoretical progresses in the field of single molecule studies. T. Strick's contribution presents a detailed description of the various micro-manipulation techniques, and reviews recent experiments on the interactions between DNA and proteins (helicases, topoisomerases, ...).
The theoretical modeling of single molecules is presented by J. Marko, with a special attention paid to the elastic and topological properties of DNA. Finally, advances in the understanding of electrophoresis, a technique of crucial importance in everyday molecular biology, are exposed in T. Duke's contribution. The third section presents provides an overview of the main computational approaches to integrate, analyse and simulate molecular and genetic networks. First, J. van Helden introduces a series of statistical and computational methods allowing the identification of short nucleic fragments putatively involved in the regulation of gene expression from sets of promoter sequences controlling co-expressed genes. Next, the chapter by Samsonova et al. connects this issue of transcriptional regulation with that of the control of cell differentiation and pattern formation during embryonic development. Finally, H. de Jong and D. Thieffry review a series of mathematical approaches to model the dynamical behaviour of complex genetic regulatory networks. This contribution includes brief descriptions and references to successful applications of these approaches, including the work of B. Novak, on the dynamical modelling of cell cycle in different model organisms, from yeast to mammals. . Provides a comprehensive overview of the structure and function of DNA and RNA at the interface between physics, biology and information science.
Local Note:
Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2017. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.
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