Nucleic acids in chemistry and biology:
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Royal Society of Chemistry
[2022]
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| Ausgabe: | 4th edition |
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| Beschreibung: | xxvi, 670 Seiten Illustrationen, Diagramme |
| ISBN: | 9781788019040 |
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| 245 | 1 | 0 | |a Nucleic acids in chemistry and biology |c edited by G. Michael Blackburn (University of Sheffield, UK), Martin Egli (Vanderbilt University, USA), Michael J. Gait (MRC Laboratory of Molecular Biology (LMB), UK) and Jonathan K. Watts (University of Massachusetts, USA) |
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Datensatz im Suchindex
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| adam_text | Contents 1 Introduction and Overview 1 G. Michael Blackburn, Martin Egli, MichaelJ. Gait and Jonathan K. Watts The Biological Importance of DNA The Origins of Nucleic Acids Research Early Structural Studies on Nucleic Acids The Discovery of the Structure of DNA The Advent of Molecular Biology The Partnership of Chemistry and Biology The Burgeoning World of RNA Frontiers in Nucleic Acids Research 1.8.1 Sequencing 1.8.2 Nucleic Acid Therapeutics 1.8.3 Gene Synthesis and Gene Editing 1.8.4 Structural Biology of Nucleic Acids References 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2 DNA and RNA Structure 2 2 3 5 9 10 13 15 15 16 17 17 18 20 Martin Egli 2.1 Structures of Components 2.1.1 Nucleosides and Nucleotides 2.1.2 Physical Properties of Nucleosides and Nucleotides 2.1.3 Spectroscopic Properties of Nucleosides and Nucleotides 2.1.4 Shapes of Nucleotides Nucleic Acids in Chemistry and Biology, 4th Edition Edited by G. Michael Blackburn, Martin Egli, Michael J. Gait and Jonathan K. Watts © The Royal Society of Chemistry 2022 Published by the Royal Society of Chemistry, www.rsc.org XV 21 22 24 27 29
xvi Contents 2.2 Standard DNA Structures 2.2.1 Primary Structure of DNA 2.2.2 Secondary Structure of DNA 2.2.3 A-DNA 2.2.4 The B-DNA Family 2.2.5 Z-DNA 2.3 Real DNA Structures 2.3.1 Sequence-dependent Modulation of DNA Structure 2.3.2 Mismatched Base-Pairs 2.3.3 Unusual DNA Structures 2.3.4 В-Z Junction 2.3.5 Circular DNA and Supercoiling 2.3.6 Triple-stranded DNA 2.3.7 Other Non-canonical DNA Structures 2.4 RNA Structure 2.4.1 Primary Structure of RNA · 2.4.2 Duplex Forms: A-RNA and A -RNA 2.4.3 RNA Secondary Structure Elements 2.4.4 Thermodynamics of Secondary Structure Elements 2.4.5 Base-Pairings in RNA 2.4.6 RNA Multiple Interactions 2.4.7 RNA Tertiary Structure 2.4.8 RNA-DNA Duplexes 2.5 Dynamics of Nucleic Acid Structures 2.5.1 Helix-Coil Transitions of Duplexes 2.5.2 Detection of Nucleic Acid Sequences by Hybridization 2.5.3 DNA Breathing 2.5.4 Energetics of the В-Z Transition 2.5.5 Rapid DNA Motions 2.6 Higher-order DNA Structures 2.6.1 Nucleosome Structure 2.6.2 Chromatin Structure 2.6.3 DNA Self-assembly and Nanotechnology References 3 Nucleosides and Nucleotides 32 32 33 37 38 39 41 41 46 48 54 55 59 61 65 65 66 68 70 71 72 72 77 79 79 82 85 85 86 86 87 ß7 90 92 96 David Μ. Williams and G. Michael Blackburn 3.1 Introduction 3.2 Chemical Synthesis of Nucleosides 3.2.1 Formation of the Glycosylic Bond 3.2.2 Building the Base onto a C-l Substituent of the Sugar 3.2.3 Building on a Preformed Imidazole Riboside 3.2.4 Transglycosylation 3.2.5 Syntheses of Base and Sugar-modified Nucleosides 97 97 98 103 107 107 108
Contents 3.3 Esters and Anhydrides of Phosphorus Oxyacids 3.3.1 Orthophosphates in Biology 3.3.2 Principles of Hydrolysis of Phosphate Esters 3.3.3 Enzyme Catalysis ofPhosphate Ester Hydrolysis 3.3.4 Enzyme Catalysis of Nucleoside Triphosphate Reactions 3.3.5 Ribozymes 3.3.6 Synthesis ofPhosphate Diesters and Monoesters 3.4 Nucleoside Esters of Polyphosphates 3.4.1 Structures of Nucleoside Polyphosphates and Co-enzymes 3.4.2 Synthesis of Nucleoside Polyphosphate Esters 3.5 Biosynthesis of Nucleotides 3.5.1 Biosynthesis of Purine Nucleotides 3.5.2 Biosynthesis of Pyrimidine Nucleotides 3.5.3 Nucleoside Diphosphates and Triphosphates 3.5.4 Deoxyribonucleotides 3.6 Catabolism of Nucleotides 3.6.1 Nucleotide Hydrolysis 3.7 Therapeutic Applications of Nucleoside Analogues 3.7.1 Anticancer Antimetabolites 3.7.2 Antiviral Chemotherapy References 4 Genes and Genomes xvii 118 118 120 123 127 130 133 137 137 141 146 147 149 151 151 152 152 154 155 157 166 170 Nicholas Rhind 4.1 Introduction 4.2 Protein-coding Genes 4.2.1 Conventional Gene Structure 4.2.2 Complex Gene Structures 4.2.3 Gene Families 4.3 Non-coding Genes 4.3.1 Non-coding Transcripts 4.3.2 Non-transcribed Genetic Elements 4.3.3 Repetitive Sequences 4.4 Chromosomes andGenomes 4.4.1 Chromosome Structure 4.4.2 Genome Structure 4.4.3 Other Independent Genetic Elements 4.5 DNA Sequence Analysis and Bioinformatics 4.5.1 Genome Sequence Analysis 4.5.2 Genome Function Analysis 4.6 DNA Transcription 4.6.1 Regulation of Eukaryotic TYanscription 4.6.2 Regulation of Prokaryotic Transcription 4.6.3 Genomic Organization of
Transcription 171 171 173 174 174 176 176 177 177 177 178 184 186 188 188 192 195 195 196 197
xviii Contents 4.7 DNA Replication 4.7.1 Replication Initiation 4.7.2 Replication Elongation 4.7.3 Telomerase and the Maintenance of Chromosome Ends 4.8 DNA Damage, Repair and Genome Rearrangement 4.8.1 Types and Consequences of DNA Damage 4.8.2 Mechanisms of DNA Repair 4.8.3 Genome Rearrangement References 5 RNA Transcription, Processing, Modification and Translation Joerg E. Braun 224 *4 5.1 RNA TYanscription 5.1.1 RNA Polymerases 5.1.2 Transcription Initiation 5.1.3 Transcription Elongation 5.1.4 Transcription Termination 5.2 RNA Processing 5.2.1 Co-transcriptional and Post-transcriptional RNA Processing 5.2.2 RNA Capping 5.2.3 RNA З -End Processing 5.2.4 RNA Splicing 5.2.5 mRNA Domain Organization and mRNP Remodelling 5.2.6 RNA Export and Transport 5.3 RNA Editing - Modification of the RNA Sequence 5.3.1 Modified Nucleotides Increase the Diversity of RNA Functional Groups 5.3.2 Base Modifications in tRNAs 5.3.3 Base Modifications in rRNA 5.3.4 A Critical Base Modification in snRNA for Spliceosome Function 5.3.5 Base Modifications in mRNA 5.4 RNAs in the Protein Factory: Translation 5.4.1 The Genetic Code 5.4.2 Ribosomes and Transfer RNAs 5.4.3 Translation of mRNA 5.4.4 Regulation of Translation and RNA Stability 5.5 Aging and Decay of mRNA References 6 198 198 203 210 211 212 213 216 219 Noncoding RNA 225 225 225 226 226 227 227 227 228 228 235 236 237 237 237 238 239 240 242 242 244 250 254 255 257 259 Scott T. Younger 6.1 Introduction to RNA-mediated Regulation of Gene Expression 6.2 Small Noncoding RNAs 6.2.1 Small Nucleolar RNAs 260 260 260
Contents 6.2.2 MicroRNAs 6.2.3 Piwi-interacting RNAs 6.3 Long Npncoding RNAs 6.3.1 Discovery of IncRNAs 6.3.2 Functions of IncRNAs 6.3.3 Biogenesis of IncRNAs 6.4 Other Noncoding RNAs 6.4.1 Enhancer RNA 6.4.2 Circular RNA 6.5 Non-human Noncoding RNAs 6.5.1 RNA as an Engine Part: The Bacteriophage Packaging Motor 6.5.2 Riboswitches References 7 Synthesis of Nucleic Acids xix 262 266 268 269 269 271 272 272 272 273 273 274 275 279 Jonathan K. Watts and MichaelJ. Gait 7.1 Chemical Synthesis of Oligodeoxyribonucleotides 7.1.1 Overall Strategy for Chemical Synthesis 7.1.2 Protected 2 -Deoxyribonucleoside Units 7.1.3 Ways of Making an Internucleotide Bond 7.1.4 Solid-phase Synthesis 7.1.5 Microarray Synthesis 7.2 Chemical Synthesis of Oligoribonucleotides 7.2.1 Protected Ribonucleoside Units 7.2.2 Oligoribonucleotide Synthesis 7.3 Synthesis of Modified Oligonucleotides 7.3.1 Modified Nucleobases 7.3.2 Modified Sugars 7.3.3 Modified Phosphates 7.3.4 Alternative Nucleic Acid Backbones - XNA 7.3.5 Modifications of Oligonucleotide 5 -and 3 -Termini 7.4 Enzymes Useful in Manipulation of Nucleic Acids 7.4.1 Polymerases and Terminal Transferases 7.4.2 Nucleases 7.4.3 Kinases and Phosphatases 7.4.4 Ligases 7.5 Enzymatic Synthesis of Oligonucleotides and RNA 7.5.1 Enzymatic Synthesis of Oligodeoxyribonucleotides 7.5.2 Enzymatic Synthesis of RNA 7.6 Enzymatic Synthesis of Genes 7.6.1 Gene Cloning 7.6.2 Classical Ligase-based Gene Synthesis 7.6.3 Polymerase-based Approaches to Gene Synthesis 7.7 Gene Mutagenesis 7.7.1 Site-directed Mutagenesis 7.7.2 Random Mutagenesis References 280 280 281
285 289 293 294 294 296 297 297 298 299 301 302 304 304 307 309 310 311 311 311 314 314 315 316 319 319 320 321
XX 8 Contents DNA and RNA Sequencing 324 MichaelJ. Booth 8.1 Introduction 8.2 Early Work in DNA Sequencing 8.2.1 Enzymatic‘Sequence by Synthesis’ 8.2.2 Sequencing by Specific Chemical Cleavage of DNA 8.3 Automated Fluorescent DNA Sequencing (First Generation) 8.3.1 Single Reaction, Fluorescent Sequencing (Conventional Sanger Sequencing) 8.3.2 Shotgun Sequencing 8.4 High-throughput DNA Sequencing (Second Generation) 8.4.1 Illumina Sequencing ֊ Cleavable Terminators and Fluorophores with On-chip Amplification 8.5 Single Molecule, Long Read DNA Sequencing (Third Generation) 8.5.1 PacBio Sequencing - Single-molecule Sequence by Synthesis in an Optical Waveguide 8.5.2 ONT Sequencing - Threading DNA Through a Nanopore 8.6 RNA Sequencing 8.6.1 Early Work in RNA Sequencing 8.6.2 Sequencing RNA via DNA 8.6.3 Direct RNA Sequencing 8.7 Counting by Sequencing 8.7.1 Chromatin Immunoprecipitation Sequencing (ChlP-Seq) 8.7.2 Gene Expression Profiling - RNA Transcriptome Sequencing 8.8 Sequencing Modified Bases 8.9 Base-calling, Errors, and Genome Assembly 8.9.1 Calling the Correct Base 8.9.2 Genome Assembly 8.10 Detection of Nucleic Acid Sequences by Hybridization 8.10.1 DNA Fingerprinting 8.10.2 DNA Microarrays 8.10.3 DNA and RNA Analysis Within a Living Cell Conflict of Interest References 9 Nucleic Acid Therapeutics 325 326 326 327 328 328 328 330 330 332 332 334 335 336 336 336 337 337 338 340 342 342 344 344 344 *345 346 347 347 350 Jonathan K. Watts 9.1 Nucleic Acid Therapeutics as Informational Drugs 9.1.1 Information and Molecular Structure in Nucleic Acids Research 9.1.2
Informational Drugs 9.2 Chemical Modifications that Enable Nucleic Acid Therapeutics 9.2.1 The Importance of Chemical Modification in Therapeutic Development 9.2.2 Sugar Modifications 9.2.3 Phosphate Modifications 351 351 352 354 354 354 358
xxi Contents 9.2.4 Total Replacement of the Sugar-Phosphate Backbone 9.2.5 Nucleobase Modifications 9.3 Antisense Oligonucleotides 9.3.1 The Antisense Principle and Proof of Concept 9.3.2 Antisense Oligonucleotides that Recruit RNase H 9.3.3 Splice Switching Using Antisense Oligonucleotides 9.3.4 Other Antisense Mechanisms 9.3.5 Delivery of Antisense Oligonucleotides 9.4 RNA Interference 9.4.1 The Biology of RNA Interference 9.4.2 RNAi Therapeutics: Delivering siRNAs and miRNAs 9.4.3 RNAi Therapeutics: Chemical Modification of siRNAs 9.4.4 Clinical Applications of RNA Interference 9.5 Immunomodulatory Effects of Oligonucleotides 9.5.1 Innate Immune Factors that Recognize Nucleic Acids 9.5.2 Immune Modulation as an Off-target Effect 9.5.3 Immune Modulation as a Therapeutic Approach 9.6 Gene Therapy 9.6.1 Principles of Gene Therapy 9.6.2 Integrating Viral Vectors 9.6.3 Non-integrating Viral Vectors 9.6.4 Nonviral Gene Therapy 9.7 mRNA Therapeutics 9.7.1 Principles of mRNA Therapeutics 9.7.2 Chemical Modification of mRNA Therapeutics 9.7.3 Optimization of mRNA Sequence and Structure 9.7.4 Applications of mRNA Therapeutics 9.8 Gene Editing by CRISPR Technology 9.8.1 The Discovery of CRISPR 9.8.2 CRISPR Technology: RNA-guided DNA Nucleases and Other Effectors 9.8.3 Reducing CRISPR to Practice References 10 In Vitro Evolution and Aptamers ЗбО 360 362 362 363 365 369 370 370 371 373 377 378 379 379 380 381 382 382 382 383 386 386 386 386 388 389 391 391 394 397 398 403 Vittorio de Franciscis, Günter Mayer and Paloma H. Giangrande Fundamentals of In Vitro Selection Advances in
Selection Methodologies Chemical Modification of Aptamers Aptamer Applications 10.4.1 Aptamers as Research Tools 10.4.2 Aptamers for Diagnostics and Imaging Applications 10.4.3 Aptamers as Therapeutics 10.4.4 Aptamers as Targeting Ligands 10.5 Clinical Studies and Therapeutic Potential of Aptamers References 10.1 10.2 10.3 10.4 404 406 407 409 409 410 411 413 415 418
xxii 11 Contents Covalent Modifications of Nucleic Acids and Their Repair 421 G. Michael Blackburn 11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 11.9 11.10 11.11 11.12 Introduction Hydrolysis of Nucleosides, Nucleotides and Nucleic Acids Reduction of Nucleosides Oxidation of Nucleosides, Nucleotides and Nucleic Acids Reactions with Nucleophiles 11.5.1 Nitrogen Nucleophiles 11.5.2 Sulfur Nucleophiles Reactions with Electrophiles 11.6.1 Halogenation of Nucleic Acid Residues 11.6.2 Reactions with Nitrogen Electrophiles 11.6.3 Reactions with Carbon Electrophiles 11.6.4 Metallation Reactions 11.6.5 Specific Reagents for Detection of Modified Bases Reactions with Metabolically Activated Carcinogens 11.7.1 Aromatic Nitrogen Heterocycles 11.7.2 N-Nitroso Compounds 11.7.3 Polycyclic Aromatic Hydrocarbons 11.7.4 Epoxidation of Natural Products Reactions with Anti-cancer Drugs 11.8.1 First Generation Alkylating Agents 11.8.2 Aziridine Antibiotics 11.8.3 Pyrrolo[l,4]benzodiazepines, P[l,4]Bs 11.8.4 Enediyne Antibiotics 11.8.5 Antibiotics Generating Superoxide Photochemical Modification of Nucleic Acids 11.9.1 Pyrimidine Photoproducts 11.9.2 Psoralen-DNA Photoproducts 11.9.3 Purine Photoproducts 11.9.4 DNA and the Ozone Barrier Effects of Ionizing Radiation on Nucleic Acids 11.10.1 Deoxyribose Products in Aerobic Solution 11.10.2 Pyrimidine Base Products 11.10.3 Purine Base Products Alkylation of Nucleic Acids and Biological Consequences 11.11.1 Exogenous Alkylation of Bases 11.11.2 Exogenous Alkylation of Phosphate Diesters 11.11.3 Endogenous Alkylation of DNA Bases 11.11.4 Endogenous
Alkylation of RNA Bases DNA Repair 11.12.1 Direct Reversal of Damage (DRD) 11.12.2 Base-Excision Repair (BER) of Altered Residues 11.12.3 Mechanisms and Inhibitors of DNA Glycohydrolases 11.12.4 Nucleotide Excision Repair (NER) 11.12.5 Base-Mismatch Repair (MMR) 422 423 423 424 424 424 425 426 426 426 426 429 431 432 433 436 436 438 439 439 440 440 442 445 446 446 449 450 452 453 453 453 455 455 456 456 457 460 462 463 464 465 468 470
Contents 11.12.6 Transcription Coupled DNA Repair 11.12.7 Repair of Covalent Damage to RNA 11.12.8 Translesion DNA Synthesis (TLS) References 12 Reversible Small Molecule-Nucleic Acid Interactions xxiii 470 471 472 474 477 W David Wilson andAnanya Paul Introduction Binding Modes and Sites of Interaction Water Interactions with Nucleic Acids The Interaction of Simple Ions with Nucleic Acids Intercalation in Nucleic Acids 12.5.1 The Classical Model 12.5.2 The Anthracycline Antibiotic Drugs 12.5.3 The Neighbour Exclusion Principle 12.5.4 Bisintercalation 12.5.5 Non-classical Intercalation: The Threading Intercalation Mode 12.6 Cooperativity in Ligand-DNA Interactions 12.7 Interactions in the Grooves of DNA 12.7.1 General Characteristics of Groove Binding 12.7.2 DAPI and Hoechst 33258 12.7.3 Netropsin and Distamycin 12.7.4 Lexitropsins 12.7.5 New Designs for Sequence-Specific Minor Groove Binders 12.7.6 Inhibition of Transcription Factor PU.l in Leukaemia by Minor Groove Binding Small Molecules 12.7.7 Small Molecules that Bind in the Major Groove of DNA 12.8 Intercalation vs. Minor Groove Binding 12.9 RNA-small Molecule Complexes 12.9.1 Streptomycin, Tuberculosis and RNA 12.9.2 Targeting of Non-ribosomal RNA 12.9.3 Methods to Assist in Discovery of New RNA-binding Small Molecules 12.9.4 Targeting the HIV-1 Frameshift Site 12.9.5 Triplet Repeat Sequences in DNA and RNA 12.9.6 Targeting Specific RNA Activity in Pathogenic Microorganisms 12.10 Small Molecule Interactions with Higher-Order Nucleic Acids 12.10.1 Triplex DNA and Its Interactions with Small Molecules 12.10.2
Quadruplex Nucleic Acids and Their Interactions with Small Molecules 12.10.3 Fluorescent Small Molecules to Monitor G-Quadruplex Binding and Occurrence in Cells 12.10.4 Four-Way DNA Structure: The Holliday Junction References 12.1 12.2 12.3 12.4 12.5 478 479 480 481 483 483 485 486 486 488 489 490 490 492 493 495 496 498 500 501 503 503 504 505 507 509 509 511 511 511 516 517 518
xxiv 13 Contents Protein-DNA Interactions 522 Ben Luisi and Elliott Stollar 13.1 Structural Features of DNA Recognized by Proteins 13.1.1 Helical Geometry 13.1.2 Sequence-dependent Conformational Effects 13.1.3 Covalent Modifications 13.2 Physical Chemistry of Protein-DNA Interactions 13.2.1 Hydrogen Bonding 13.2.2 Salt Bridges 13.2.3 The Hydrophobic Effect 13.2.4 Additional Roles of Water 13.2.5 Van der Waals Interactions and Base-Stacking 13.3 Representative DNA Recognition Motifs in Proteins 13.3.1 Protein Structural Elements for DNA Recognition 13.3.2 Structural Economy of α-Helical Motifs 13.3.3 Zinc-bearing Motifs 13.3.4 Orientations of a-Helices in the DNA Major Groove 13.3.5 Minor Groove Recognition with a-Helices 13.3.6 ß-Motifs 13.3.7 Loops and Flexible Elements 13.3.8 Single-stranded DNA Recognition 13.3.9 Four-stranded DNA Recognition 13.4 Kinetic and Thermodynamic Aspects of Protein-DNA Interactions 13.4.1 The Delicate Balance of Sequence Specificity 13.4.2 Specific Versus Non-Specific Complexes 13.4.3 Electrostatics 13.4.4 DNA Conformational Adaptability 13.4.5 Cooperativity Through Protein-Protein and DNA-Protein Interactions 13.4.6 Kinetic and Non-equilibrium Aspects of DNA Recognition 13.4.7 Conformational Flexibility, Compartmentalization and Liquid-Liquid Phase Separation * 550 13.5 Specificity of DNA Enzymes 13.5.1 Restriction Enzymes: Recognition via the Transition State 13.5.2 DNA Repair Endonucleases and Glycosylases 13.5.3 Photochemistry of Photolyases 13.5.4 Structure-selective Nucleases 13.6 Packaging DNA and Its Biological Function 13.6.1
Nucleosomes and Chromatin of the Eukaryotes 13.6.2 Packaging and Architectural Proteins in Archaebacteria and Eubacteria 13.7 DNA-directed Polymerases 13.7.1 DNA-directed DNA Polymerases 13.7.2 DNA-directed RNA Polymerases 13.8 Nanomachines that Manipulate Duplex DNA 13.8.1 Helicases 13.8.2 DNA Pumps 13.8.3 DNA Topoisomerases 13.9 Future Perspectives References 523 523 527 527 528 528 530 531 531 532 533 533 534 536 537 538 538 540 540 542 543 543 544 545 546 547 549 551 551 553 555 555 556 556 559 560 560 561 563 563 565 566 567 570
Contents 14 RNA-Protein Interactions xxv 572 Michael E. Harris 14.1 Characteristic Features of RNA Binding Proteins 14.1.1 Structural Features of RNA Recognized by Protein 14.1.2 Chemical Basis of Protein-RNA Interactions 14.1.3 Thermodynamics of RNA-Protein Interactions 14.1.4 RNA Binding Domains - Specialized Protein Motifs that Bind RNA 14.2 Specificity in Protein-RNA Interactions 14.2.1 Transcriptomic and Proteomic Analyses of RBP Specificity 14.2.2 Affinity Distributions - Toward Comprehensive Descriptions of Specificity 14.2.3 Mechanisms Modulating RBP Specificity 14.3 Roles of RNA Binding Domains in Enzyme Function 14.3.1 Base-specific Recognition and Cleavage of ssRNA by Ribonucleases A and T1 14.3.2 The Specificity and Function of Ribonuclease III Enzymes Involves Multiple RBDs 14.3.3 Aminoacyl Transfer RNA Synthetases: Shape and Sequence Recognition of tRNA 14.3.4 RNA Binding and Remodelling by Helicases 14.4 RNA Binding Proteins in Biotechnology and Biomedicine 14.4.1 RBPs Associated with Human Diseases 14.4.2 Inhibition of RBP-RNA Interactions with Small Molecules 14.4.3 Applying Principles of RBP Affinity and Specificity: Engineering Synthetic mRNAs as Vaccines 14.4.4 The Future References 15 Online Content: Physical and Structural Techniques Applied to Nucleic Acids Yitzhak Tor, Kalle Gehring, Daniele Fabris, Martin Egli, Andrei A. Korostelev, Timothy D. Craggs, Alice Pyne, Keith T. Gagnon, Jonathan К Watts, Thomas E. Cheatham III and Nigel G.J. Richards 15.1 Spectroscopic Techniques 15.1.1 UV Absorption 15.1.2 Fluorescence 15.1.3 Circular and Linear Dichroism
15.1.4 Infrared and Raman Spectroscopy 15.2 Nuclear Magnetic Resonance 15.3 Mass Spectrometry 15.3.1 Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 15.3.2 Electrospray Ionization Mass Spectrometry 15.4 Diffraction Techniques 15,4.1 Fibre Diffraction 15.4.2 Single Crystal X-ray Crystallography 573 574 575 576 578 589 590 593 595 599 599 601 605 606 608 608 614 619 621 624
xxvi 15.4.3 Neutron Diffraction 15.4.4 Electron Diffraction 15.5 Cryogenic Electron Microscopy (Cryo-EM) 15.5.1 The Basics of Cryo-EM 15.5.2 Brief History and Recent Advances that Propelled Cryo-EM as a Method 15.5.3 The Power of Single-Particle Cryo-EM: High Resolution and Structural Ensembles Resolve Individual Nucleotides and Reconstruct Molecular Mechanisms 15.5.4 Negative-Stain EM and Electron Tomography 15.6 Optical Microscopy of Nucleic Acids 15.6.1 Fluorescence Microscopy of Nucleic Acids 15.6.2 Fluorescence In Situ Hybridization (FISH) 15.6.3 Super-Resolution Microscopy - DNA-Paint 15.6.4 Förster Resonance Energy Transfer (FRET) in Nucleic Acids 15.7 Atomic Force Microscopy 15.8 Electrophoresis 15.8.1 Principles of Electrophoresis 15.8.2 Electrophoresis and Topology 15.8.3 Electrophoretic Mobility Shift Assay (EMSA) 15.8.4 Pulsed Field Electrophoresis 15.8.5 Capillary Electrophoresis 15.9 Chromatographic Methods 15.9.1 Reverse-Phase HPLC 15.9.2 Ion-Exchange HPLC 15.9.3 Size-Exclusion Chromatography 15.10 Centrifugation 15.11 Light Scattering Techniques 15.11.1 Static Light Scattering 15.11.2 Dynamic Light Scattering 15.11.3 Small Angle X-ray Scattering 15.12 Thermodynamic Analysis of Nucleic Acids 15.12.1 UV Melting Assay 15.12.2 Calorimetry 15.13 Molecular Mechanics and Dynamics 15.13.1 Molecular Mechanics and Nucleic Acid Force Fields 15.13.2 Conformational Ensemble and Energy Minimization 15.13.3 Molecular Dynamics Can Elucidate the Full Conformational Ensemble 15.14 QM/MM Methods for Modelling Nucleic Acids Reactions 15.14.1 Overview of the QM/MM Method 15.14.2
QM/MM Studies of DNA Repair References Glossary Շ27 G. Μ. Blackburn, Μ. Egli, M. J. Gait, K. Gehring, N. Rhind andJ. К Watts Subject Index 648
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Contents 1 Introduction and Overview 1 G. Michael Blackburn, Martin Egli, MichaelJ. Gait and Jonathan K. Watts The Biological Importance of DNA The Origins of Nucleic Acids Research Early Structural Studies on Nucleic Acids The Discovery of the Structure of DNA The Advent of Molecular Biology The Partnership of Chemistry and Biology The Burgeoning World of RNA Frontiers in Nucleic Acids Research 1.8.1 Sequencing 1.8.2 Nucleic Acid Therapeutics 1.8.3 Gene Synthesis and Gene Editing 1.8.4 Structural Biology of Nucleic Acids References 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2 DNA and RNA Structure 2 2 3 5 9 10 13 15 15 16 17 17 18 20 Martin Egli 2.1 Structures of Components 2.1.1 Nucleosides and Nucleotides 2.1.2 Physical Properties of Nucleosides and Nucleotides 2.1.3 Spectroscopic Properties of Nucleosides and Nucleotides 2.1.4 Shapes of Nucleotides Nucleic Acids in Chemistry and Biology, 4th Edition Edited by G. Michael Blackburn, Martin Egli, Michael J. Gait and Jonathan K. Watts © The Royal Society of Chemistry 2022 Published by the Royal Society of Chemistry, www.rsc.org XV 21 22 24 27 29
xvi Contents 2.2 Standard DNA Structures 2.2.1 Primary Structure of DNA 2.2.2 Secondary Structure of DNA 2.2.3 A-DNA 2.2.4 The B-DNA Family 2.2.5 Z-DNA 2.3 Real DNA Structures 2.3.1 Sequence-dependent Modulation of DNA Structure 2.3.2 Mismatched Base-Pairs 2.3.3 Unusual DNA Structures 2.3.4 В-Z Junction 2.3.5 Circular DNA and Supercoiling 2.3.6 Triple-stranded DNA 2.3.7 Other Non-canonical DNA Structures 2.4 RNA Structure 2.4.1 Primary Structure of RNA '· 2.4.2 Duplex Forms: A-RNA and A'-RNA 2.4.3 RNA Secondary Structure Elements 2.4.4 Thermodynamics of Secondary Structure Elements 2.4.5 Base-Pairings in RNA 2.4.6 RNA Multiple Interactions 2.4.7 RNA Tertiary Structure 2.4.8 RNA-DNA Duplexes 2.5 Dynamics of Nucleic Acid Structures 2.5.1 Helix-Coil Transitions of Duplexes 2.5.2 Detection of Nucleic Acid Sequences by Hybridization 2.5.3 DNA Breathing 2.5.4 Energetics of the В-Z Transition 2.5.5 Rapid DNA Motions 2.6 Higher-order DNA Structures 2.6.1 Nucleosome Structure 2.6.2 Chromatin Structure 2.6.3 DNA Self-assembly and Nanotechnology References 3 Nucleosides and Nucleotides 32 32 33 37 38 39 41 41 46 48 54 55 59 61 65 65 66 68 70 71 72 72 77 79 79 82 85 85 86 86 87 ß7 90 92 96 David Μ. Williams and G. Michael Blackburn 3.1 Introduction 3.2 Chemical Synthesis of Nucleosides 3.2.1 Formation of the Glycosylic Bond 3.2.2 Building the Base onto a C-l Substituent of the Sugar 3.2.3 Building on a Preformed Imidazole Riboside 3.2.4 Transglycosylation 3.2.5 Syntheses of Base and Sugar-modified Nucleosides 97 97 98 103 107 107 108
Contents 3.3 Esters and Anhydrides of Phosphorus Oxyacids 3.3.1 Orthophosphates in Biology 3.3.2 Principles of Hydrolysis of Phosphate Esters 3.3.3 Enzyme Catalysis ofPhosphate Ester Hydrolysis 3.3.4 Enzyme Catalysis of Nucleoside Triphosphate Reactions 3.3.5 Ribozymes 3.3.6 Synthesis ofPhosphate Diesters and Monoesters 3.4 Nucleoside Esters of Polyphosphates 3.4.1 Structures of Nucleoside Polyphosphates and Co-enzymes 3.4.2 Synthesis of Nucleoside Polyphosphate Esters 3.5 Biosynthesis of Nucleotides 3.5.1 Biosynthesis of Purine Nucleotides 3.5.2 Biosynthesis of Pyrimidine Nucleotides 3.5.3 Nucleoside Diphosphates and Triphosphates 3.5.4 Deoxyribonucleotides 3.6 Catabolism of Nucleotides 3.6.1 Nucleotide Hydrolysis 3.7 Therapeutic Applications of Nucleoside Analogues 3.7.1 Anticancer Antimetabolites 3.7.2 Antiviral Chemotherapy References 4 Genes and Genomes xvii 118 118 120 123 127 130 133 137 137 141 146 147 149 151 151 152 152 154 155 157 166 170 Nicholas Rhind 4.1 Introduction 4.2 Protein-coding Genes 4.2.1 Conventional Gene Structure 4.2.2 Complex Gene Structures 4.2.3 Gene Families 4.3 Non-coding Genes 4.3.1 Non-coding Transcripts 4.3.2 Non-transcribed Genetic Elements 4.3.3 Repetitive Sequences 4.4 Chromosomes andGenomes 4.4.1 Chromosome Structure 4.4.2 Genome Structure 4.4.3 Other Independent Genetic Elements 4.5 DNA Sequence Analysis and Bioinformatics 4.5.1 Genome Sequence Analysis 4.5.2 Genome Function Analysis 4.6 DNA Transcription 4.6.1 Regulation of Eukaryotic TYanscription 4.6.2 Regulation of Prokaryotic Transcription 4.6.3 Genomic Organization of
Transcription 171 171 173 174 174 176 176 177 177 177 178 184 186 188 188 192 195 195 196 197
xviii Contents 4.7 DNA Replication 4.7.1 Replication Initiation 4.7.2 Replication Elongation 4.7.3 Telomerase and the Maintenance of Chromosome Ends 4.8 DNA Damage, Repair and Genome Rearrangement 4.8.1 Types and Consequences of DNA Damage 4.8.2 Mechanisms of DNA Repair 4.8.3 Genome Rearrangement References 5 RNA Transcription, Processing, Modification and Translation Joerg E. Braun 224 *4 5.1 RNA TYanscription 5.1.1 RNA Polymerases 5.1.2 Transcription Initiation 5.1.3 Transcription Elongation 5.1.4 Transcription Termination 5.2 RNA Processing 5.2.1 Co-transcriptional and Post-transcriptional RNA Processing 5.2.2 RNA Capping 5.2.3 RNA З'-End Processing 5.2.4 RNA Splicing 5.2.5 mRNA Domain Organization and mRNP Remodelling 5.2.6 RNA Export and Transport 5.3 RNA Editing - Modification of the RNA Sequence 5.3.1 Modified Nucleotides Increase the Diversity of RNA Functional Groups 5.3.2 Base Modifications in tRNAs 5.3.3 Base Modifications in rRNA 5.3.4 A Critical Base Modification in snRNA for Spliceosome Function 5.3.5 Base Modifications in mRNA 5.4 RNAs in the Protein Factory: Translation 5.4.1 The Genetic Code 5.4.2 Ribosomes and Transfer RNAs 5.4.3 Translation of mRNA 5.4.4 Regulation of Translation and RNA Stability 5.5 Aging and Decay of mRNA References 6 198 198 203 210 211 212 213 216 219 Noncoding RNA 225 225 225 226 226 227 227 227 228 228 235 236 237 237 237 238 239 240 242 242 244 250 254 255 257 259 Scott T. Younger 6.1 Introduction to RNA-mediated Regulation of Gene Expression 6.2 Small Noncoding RNAs 6.2.1 Small Nucleolar RNAs 260 260 260
Contents 6.2.2 MicroRNAs 6.2.3 Piwi-interacting RNAs 6.3 Long Npncoding RNAs 6.3.1 Discovery of IncRNAs 6.3.2 Functions of IncRNAs 6.3.3 Biogenesis of IncRNAs 6.4 Other Noncoding RNAs 6.4.1 Enhancer RNA 6.4.2 Circular RNA 6.5 Non-human Noncoding RNAs 6.5.1 RNA as an Engine Part: The Bacteriophage Packaging Motor 6.5.2 Riboswitches References 7 Synthesis of Nucleic Acids xix 262 266 268 269 269 271 272 272 272 273 273 274 275 279 Jonathan K. Watts and MichaelJ. Gait 7.1 Chemical Synthesis of Oligodeoxyribonucleotides 7.1.1 Overall Strategy for Chemical Synthesis 7.1.2 Protected 2'-Deoxyribonucleoside Units 7.1.3 Ways of Making an Internucleotide Bond 7.1.4 Solid-phase Synthesis 7.1.5 Microarray Synthesis 7.2 Chemical Synthesis of Oligoribonucleotides 7.2.1 Protected Ribonucleoside Units 7.2.2 Oligoribonucleotide Synthesis 7.3 Synthesis of Modified Oligonucleotides 7.3.1 Modified Nucleobases 7.3.2 Modified Sugars 7.3.3 Modified Phosphates 7.3.4 Alternative Nucleic Acid Backbones - XNA 7.3.5 Modifications of Oligonucleotide 5'-and 3'-Termini 7.4 Enzymes Useful in Manipulation of Nucleic Acids 7.4.1 Polymerases and Terminal Transferases 7.4.2 Nucleases 7.4.3 Kinases and Phosphatases 7.4.4 Ligases 7.5 Enzymatic Synthesis of Oligonucleotides and RNA 7.5.1 Enzymatic Synthesis of Oligodeoxyribonucleotides 7.5.2 Enzymatic Synthesis of RNA 7.6 Enzymatic Synthesis of Genes 7.6.1 Gene Cloning 7.6.2 Classical Ligase-based Gene Synthesis 7.6.3 Polymerase-based Approaches to Gene Synthesis 7.7 Gene Mutagenesis 7.7.1 Site-directed Mutagenesis 7.7.2 Random Mutagenesis References 280 280 281
285 289 293 294 294 296 297 297 298 299 301 302 304 304 307 309 310 311 311 311 314 314 315 316 319 319 320 321
XX 8 Contents DNA and RNA Sequencing 324 MichaelJ. Booth 8.1 Introduction 8.2 Early Work in DNA Sequencing 8.2.1 Enzymatic‘Sequence by Synthesis’ 8.2.2 Sequencing by Specific Chemical Cleavage of DNA 8.3 Automated Fluorescent DNA Sequencing (First Generation) 8.3.1 Single Reaction, Fluorescent Sequencing (Conventional Sanger Sequencing) 8.3.2 Shotgun Sequencing 8.4 High-throughput DNA Sequencing (Second Generation) 8.4.1 Illumina Sequencing ֊ Cleavable Terminators and Fluorophores with On-chip Amplification 8.5 Single Molecule, Long Read DNA Sequencing (Third Generation) 8.5.1 PacBio Sequencing - Single-molecule Sequence by Synthesis in an Optical Waveguide 8.5.2 ONT Sequencing - Threading DNA Through a Nanopore 8.6 RNA Sequencing 8.6.1 Early Work in RNA Sequencing 8.6.2 Sequencing RNA via DNA 8.6.3 Direct RNA Sequencing 8.7 Counting by Sequencing 8.7.1 Chromatin Immunoprecipitation Sequencing (ChlP-Seq) 8.7.2 Gene Expression Profiling - RNA Transcriptome Sequencing 8.8 Sequencing Modified Bases 8.9 Base-calling, Errors, and Genome Assembly 8.9.1 Calling the Correct Base 8.9.2 Genome Assembly 8.10 Detection of Nucleic Acid Sequences by Hybridization 8.10.1 DNA Fingerprinting 8.10.2 DNA Microarrays 8.10.3 DNA and RNA Analysis Within a Living Cell Conflict of Interest References 9 Nucleic Acid Therapeutics 325 326 326 327 328 328 328 330 330 332 332 334 335 336 336 336 337 337 338 340 342 342 344 344 344 *345 346 347 347 350 Jonathan K. Watts 9.1 Nucleic Acid Therapeutics as Informational Drugs 9.1.1 Information and Molecular Structure in Nucleic Acids Research 9.1.2
Informational Drugs 9.2 Chemical Modifications that Enable Nucleic Acid Therapeutics 9.2.1 The Importance of Chemical Modification in Therapeutic Development 9.2.2 Sugar Modifications 9.2.3 Phosphate Modifications 351 351 352 354 354 354 358
xxi Contents 9.2.4 Total Replacement of the Sugar-Phosphate Backbone 9.2.5 Nucleobase Modifications 9.3 Antisense Oligonucleotides 9.3.1 The Antisense Principle and Proof of Concept 9.3.2 Antisense Oligonucleotides that Recruit RNase H 9.3.3 Splice Switching Using Antisense Oligonucleotides 9.3.4 Other Antisense Mechanisms 9.3.5 Delivery of Antisense Oligonucleotides 9.4 RNA Interference 9.4.1 The Biology of RNA Interference 9.4.2 RNAi Therapeutics: Delivering siRNAs and miRNAs 9.4.3 RNAi Therapeutics: Chemical Modification of siRNAs 9.4.4 Clinical Applications of RNA Interference 9.5 Immunomodulatory Effects of Oligonucleotides 9.5.1 Innate Immune Factors that Recognize Nucleic Acids 9.5.2 Immune Modulation as an Off-target Effect 9.5.3 Immune Modulation as a Therapeutic Approach 9.6 Gene Therapy 9.6.1 Principles of Gene Therapy 9.6.2 Integrating Viral Vectors 9.6.3 Non-integrating Viral Vectors 9.6.4 Nonviral Gene Therapy 9.7 mRNA Therapeutics 9.7.1 Principles of mRNA Therapeutics 9.7.2 Chemical Modification of mRNA Therapeutics 9.7.3 Optimization of mRNA Sequence and Structure 9.7.4 Applications of mRNA Therapeutics 9.8 Gene Editing by CRISPR Technology 9.8.1 The Discovery of CRISPR 9.8.2 CRISPR Technology: RNA-guided DNA Nucleases and Other Effectors 9.8.3 Reducing CRISPR to Practice References 10 In Vitro Evolution and Aptamers ЗбО 360 362 362 363 365 369 370 370 371 373 377 378 379 379 380 381 382 382 382 383 386 386 386 386 388 389 391 391 394 397 398 403 Vittorio de Franciscis, Günter Mayer and Paloma H. Giangrande Fundamentals of In Vitro Selection Advances in
Selection Methodologies Chemical Modification of Aptamers Aptamer Applications 10.4.1 Aptamers as Research Tools 10.4.2 Aptamers for Diagnostics and Imaging Applications 10.4.3 Aptamers as Therapeutics 10.4.4 Aptamers as Targeting Ligands 10.5 Clinical Studies and Therapeutic Potential of Aptamers References 10.1 10.2 10.3 10.4 404 406 407 409 409 410 411 413 415 418
xxii 11 Contents Covalent Modifications of Nucleic Acids and Their Repair 421 G. Michael Blackburn 11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 11.9 11.10 11.11 11.12 Introduction Hydrolysis of Nucleosides, Nucleotides and Nucleic Acids Reduction of Nucleosides Oxidation of Nucleosides, Nucleotides and Nucleic Acids Reactions with Nucleophiles 11.5.1 Nitrogen Nucleophiles 11.5.2 Sulfur Nucleophiles Reactions with Electrophiles 11.6.1 Halogenation of Nucleic Acid Residues 11.6.2 Reactions with Nitrogen Electrophiles 11.6.3 Reactions with Carbon Electrophiles 11.6.4 Metallation Reactions 11.6.5 Specific Reagents for Detection of Modified Bases Reactions with Metabolically Activated Carcinogens 11.7.1 Aromatic Nitrogen Heterocycles 11.7.2 N-Nitroso Compounds 11.7.3 Polycyclic Aromatic Hydrocarbons 11.7.4 Epoxidation of Natural Products Reactions with Anti-cancer Drugs 11.8.1 First Generation Alkylating Agents 11.8.2 Aziridine Antibiotics 11.8.3 Pyrrolo[l,4]benzodiazepines, P[l,4]Bs 11.8.4 Enediyne Antibiotics 11.8.5 Antibiotics Generating Superoxide Photochemical Modification of Nucleic Acids 11.9.1 Pyrimidine Photoproducts 11.9.2 Psoralen-DNA Photoproducts 11.9.3 Purine Photoproducts 11.9.4 DNA and the Ozone Barrier Effects of Ionizing Radiation on Nucleic Acids 11.10.1 Deoxyribose Products in Aerobic Solution 11.10.2 Pyrimidine Base Products 11.10.3 Purine Base Products Alkylation of Nucleic Acids and Biological Consequences 11.11.1 Exogenous Alkylation of Bases 11.11.2 Exogenous Alkylation of Phosphate Diesters 11.11.3 Endogenous Alkylation of DNA Bases 11.11.4 Endogenous
Alkylation of RNA Bases DNA Repair 11.12.1 Direct Reversal of Damage (DRD) 11.12.2 Base-Excision Repair (BER) of Altered Residues 11.12.3 Mechanisms and Inhibitors of DNA Glycohydrolases 11.12.4 Nucleotide Excision Repair (NER) 11.12.5 Base-Mismatch Repair (MMR) 422 423 423 424 424 424 425 426 426 426 426 429 431 432 433 436 436 438 439 439 440 440 442 445 446 446 449 450 452 453 453 453 455 455 456 456 457 460 462 463 464 465 468 470
Contents 11.12.6 Transcription Coupled DNA Repair 11.12.7 Repair of Covalent Damage to RNA 11.12.8 Translesion DNA Synthesis (TLS) References 12 Reversible Small Molecule-Nucleic Acid Interactions xxiii 470 471 472 474 477 W David Wilson andAnanya Paul Introduction Binding Modes and Sites of Interaction Water Interactions with Nucleic Acids The Interaction of Simple Ions with Nucleic Acids Intercalation in Nucleic Acids 12.5.1 The Classical Model 12.5.2 The Anthracycline Antibiotic Drugs 12.5.3 The Neighbour Exclusion Principle 12.5.4 Bisintercalation 12.5.5 Non-classical Intercalation: The Threading Intercalation Mode 12.6 Cooperativity in Ligand-DNA Interactions 12.7 Interactions in the Grooves of DNA 12.7.1 General Characteristics of Groove Binding 12.7.2 DAPI and Hoechst 33258 12.7.3 Netropsin and Distamycin 12.7.4 Lexitropsins 12.7.5 New Designs for Sequence-Specific Minor Groove Binders 12.7.6 Inhibition of Transcription Factor PU.l in Leukaemia by Minor Groove Binding Small Molecules 12.7.7 Small Molecules that Bind in the Major Groove of DNA 12.8 Intercalation vs. Minor Groove Binding 12.9 RNA-small Molecule Complexes 12.9.1 Streptomycin, Tuberculosis and RNA 12.9.2 Targeting of Non-ribosomal RNA 12.9.3 Methods to Assist in Discovery of New RNA-binding Small Molecules 12.9.4 Targeting the HIV-1 Frameshift Site 12.9.5 Triplet Repeat Sequences in DNA and RNA 12.9.6 Targeting Specific RNA Activity in Pathogenic Microorganisms 12.10 Small Molecule Interactions with Higher-Order Nucleic Acids 12.10.1 Triplex DNA and Its Interactions with Small Molecules 12.10.2
Quadruplex Nucleic Acids and Their Interactions with Small Molecules 12.10.3 Fluorescent Small Molecules to Monitor G-Quadruplex Binding and Occurrence in Cells 12.10.4 Four-Way DNA Structure: The Holliday Junction References 12.1 12.2 12.3 12.4 12.5 478 479 480 481 483 483 485 486 486 488 489 490 490 492 493 495 496 498 500 501 503 503 504 505 507 509 509 511 511 511 516 517 518
xxiv 13 Contents Protein-DNA Interactions 522 Ben Luisi and Elliott Stollar 13.1 Structural Features of DNA Recognized by Proteins 13.1.1 Helical Geometry 13.1.2 Sequence-dependent Conformational Effects 13.1.3 Covalent Modifications 13.2 Physical Chemistry of Protein-DNA Interactions 13.2.1 Hydrogen Bonding 13.2.2 Salt Bridges 13.2.3 The Hydrophobic Effect 13.2.4 Additional Roles of Water 13.2.5 Van der Waals Interactions and Base-Stacking 13.3 Representative DNA Recognition Motifs in Proteins 13.3.1 Protein Structural Elements for DNA Recognition 13.3.2 Structural Economy of α-Helical Motifs 13.3.3 Zinc-bearing Motifs 13.3.4 Orientations of a-Helices in the DNA Major Groove 13.3.5 Minor Groove Recognition with a-Helices 13.3.6 ß-Motifs 13.3.7 Loops and Flexible Elements 13.3.8 Single-stranded DNA Recognition 13.3.9 Four-stranded DNA Recognition 13.4 Kinetic and Thermodynamic Aspects of Protein-DNA Interactions 13.4.1 The Delicate Balance of Sequence Specificity 13.4.2 Specific Versus Non-Specific Complexes 13.4.3 Electrostatics 13.4.4 DNA Conformational Adaptability 13.4.5 Cooperativity Through Protein-Protein and DNA-Protein Interactions 13.4.6 Kinetic and Non-equilibrium Aspects of DNA Recognition 13.4.7 Conformational Flexibility, Compartmentalization and Liquid-Liquid Phase Separation * 550 13.5 Specificity of DNA Enzymes 13.5.1 Restriction Enzymes: Recognition via the Transition State 13.5.2 DNA Repair Endonucleases and Glycosylases 13.5.3 Photochemistry of Photolyases 13.5.4 Structure-selective Nucleases 13.6 Packaging DNA and Its Biological Function 13.6.1
Nucleosomes and Chromatin of the Eukaryotes 13.6.2 Packaging and Architectural Proteins in Archaebacteria and Eubacteria 13.7 DNA-directed Polymerases 13.7.1 DNA-directed DNA Polymerases 13.7.2 DNA-directed RNA Polymerases 13.8 Nanomachines that Manipulate Duplex DNA 13.8.1 Helicases 13.8.2 DNA Pumps 13.8.3 DNA Topoisomerases 13.9 Future Perspectives References 523 523 527 527 528 528 530 531 531 532 533 533 534 536 537 538 538 540 540 542 543 543 544 545 546 547 549 551 551 553 555 555 556 556 559 560 560 561 563 563 565 566 567 570
Contents 14 RNA-Protein Interactions xxv 572 Michael E. Harris 14.1 Characteristic Features of RNA Binding Proteins 14.1.1 Structural Features of RNA Recognized by Protein 14.1.2 Chemical Basis of Protein-RNA Interactions 14.1.3 Thermodynamics of RNA-Protein Interactions 14.1.4 RNA Binding Domains - Specialized Protein Motifs that Bind RNA 14.2 Specificity in Protein-RNA Interactions 14.2.1 Transcriptomic and Proteomic Analyses of RBP Specificity 14.2.2 Affinity Distributions - Toward Comprehensive Descriptions of Specificity 14.2.3 Mechanisms Modulating RBP Specificity 14.3 Roles of RNA Binding Domains in Enzyme Function 14.3.1 Base-specific Recognition and Cleavage of ssRNA by Ribonucleases A and T1 14.3.2 The Specificity and Function of Ribonuclease III Enzymes Involves Multiple RBDs 14.3.3 Aminoacyl Transfer RNA Synthetases: Shape and Sequence Recognition of tRNA 14.3.4 RNA Binding and Remodelling by Helicases 14.4 RNA Binding Proteins in Biotechnology and Biomedicine 14.4.1 RBPs Associated with Human Diseases 14.4.2 Inhibition of RBP-RNA Interactions with Small Molecules 14.4.3 Applying Principles of RBP Affinity and Specificity: Engineering Synthetic mRNAs as Vaccines 14.4.4 The Future References 15 Online Content: Physical and Structural Techniques Applied to Nucleic Acids Yitzhak Tor, Kalle Gehring, Daniele Fabris, Martin Egli, Andrei A. Korostelev, Timothy D. Craggs, Alice Pyne, Keith T. Gagnon, Jonathan К Watts, Thomas E. Cheatham III and Nigel G.J. Richards 15.1 Spectroscopic Techniques 15.1.1 UV Absorption 15.1.2 Fluorescence 15.1.3 Circular and Linear Dichroism
15.1.4 Infrared and Raman Spectroscopy 15.2 Nuclear Magnetic Resonance 15.3 Mass Spectrometry 15.3.1 Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 15.3.2 Electrospray Ionization Mass Spectrometry 15.4 Diffraction Techniques 15,4.1 Fibre Diffraction 15.4.2 Single Crystal X-ray Crystallography 573 574 575 576 578 589 590 593 595 599 599 601 605 606 608 608 614 619 621 624
xxvi 15.4.3 Neutron Diffraction 15.4.4 Electron Diffraction 15.5 Cryogenic Electron Microscopy (Cryo-EM) 15.5.1 The Basics of Cryo-EM 15.5.2 Brief History and Recent Advances that Propelled Cryo-EM as a Method 15.5.3 The Power of Single-Particle Cryo-EM: High Resolution and Structural Ensembles Resolve Individual Nucleotides and Reconstruct Molecular Mechanisms 15.5.4 Negative-Stain EM and Electron Tomography 15.6 Optical Microscopy of Nucleic Acids 15.6.1 Fluorescence Microscopy of Nucleic Acids 15.6.2 Fluorescence In Situ Hybridization (FISH) 15.6.3 Super-Resolution Microscopy - DNA-Paint 15.6.4 Förster Resonance Energy Transfer (FRET) in Nucleic Acids 15.7 Atomic Force Microscopy 15.8 Electrophoresis 15.8.1 Principles of Electrophoresis 15.8.2 Electrophoresis and Topology 15.8.3 Electrophoretic Mobility Shift Assay (EMSA) 15.8.4 Pulsed Field Electrophoresis 15.8.5 Capillary Electrophoresis 15.9 Chromatographic Methods 15.9.1 Reverse-Phase HPLC 15.9.2 Ion-Exchange HPLC 15.9.3 Size-Exclusion Chromatography 15.10 Centrifugation 15.11 Light Scattering Techniques 15.11.1 Static Light Scattering 15.11.2 Dynamic Light Scattering 15.11.3 Small Angle X-ray Scattering 15.12 Thermodynamic Analysis of Nucleic Acids 15.12.1 UV Melting Assay 15.12.2 Calorimetry 15.13 Molecular Mechanics and Dynamics 15.13.1 Molecular Mechanics and Nucleic Acid Force Fields 15.13.2 Conformational Ensemble and Energy Minimization 15.13.3 Molecular Dynamics Can Elucidate the Full Conformational Ensemble 15.14 QM/MM Methods for Modelling Nucleic Acids Reactions 15.14.1 Overview of the QM/MM Method 15.14.2
QM/MM Studies of DNA Repair References Glossary Շ27 G. Μ. Blackburn, Μ. Egli, M. J. Gait, K. Gehring, N. Rhind andJ. К Watts Subject Index 648 |
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| genre | (DE-588)4143413-4 Aufsatzsammlung gnd-content |
| genre_facet | Aufsatzsammlung |
| id | DE-604.BV048310477 |
| illustrated | Illustrated |
| index_date | 2024-07-03T20:09:19Z |
| indexdate | 2024-07-10T09:34:55Z |
| institution | BVB |
| isbn | 9781788019040 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-033690073 |
| oclc_num | 1344263504 |
| open_access_boolean | |
| owner | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-11 DE-19 DE-BY-UBM |
| owner_facet | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-11 DE-19 DE-BY-UBM |
| physical | xxvi, 670 Seiten Illustrationen, Diagramme |
| publishDate | 2022 |
| publishDateSearch | 2022 |
| publishDateSort | 2022 |
| publisher | Royal Society of Chemistry |
| record_format | marc |
| spelling | Nucleic acids in chemistry and biology edited by G. Michael Blackburn (University of Sheffield, UK), Martin Egli (Vanderbilt University, USA), Michael J. Gait (MRC Laboratory of Molecular Biology (LMB), UK) and Jonathan K. Watts (University of Massachusetts, USA) 4th edition Cambridge Royal Society of Chemistry [2022] xxvi, 670 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Nucleinsäuren Nucleic Acids Nucleinsäuren (DE-588)4172117-2 gnd rswk-swf Biochemie (DE-588)4006777-4 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Nucleinsäuren (DE-588)4172117-2 s Biochemie (DE-588)4006777-4 s DE-604 Blackburn, G. Michael (DE-588)1265688710 edt Egli, Martin 1961- (DE-588)1046651471 edt Gait, Michael J. (DE-588)1265688885 edt Watts, Jonathan K. (DE-588)1265689067 edt Erscheint auch als Online-Ausgabe, EPUB 978-1-83916-324-1 Digitalisierung UB Regensburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=033690073&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Nucleic acids in chemistry and biology Nucleinsäuren Nucleic Acids Nucleinsäuren (DE-588)4172117-2 gnd Biochemie (DE-588)4006777-4 gnd |
| subject_GND | (DE-588)4172117-2 (DE-588)4006777-4 (DE-588)4143413-4 |
| title | Nucleic acids in chemistry and biology |
| title_auth | Nucleic acids in chemistry and biology |
| title_exact_search | Nucleic acids in chemistry and biology |
| title_exact_search_txtP | Nucleic acids in chemistry and biology |
| title_full | Nucleic acids in chemistry and biology edited by G. Michael Blackburn (University of Sheffield, UK), Martin Egli (Vanderbilt University, USA), Michael J. Gait (MRC Laboratory of Molecular Biology (LMB), UK) and Jonathan K. Watts (University of Massachusetts, USA) |
| title_fullStr | Nucleic acids in chemistry and biology edited by G. Michael Blackburn (University of Sheffield, UK), Martin Egli (Vanderbilt University, USA), Michael J. Gait (MRC Laboratory of Molecular Biology (LMB), UK) and Jonathan K. Watts (University of Massachusetts, USA) |
| title_full_unstemmed | Nucleic acids in chemistry and biology edited by G. Michael Blackburn (University of Sheffield, UK), Martin Egli (Vanderbilt University, USA), Michael J. Gait (MRC Laboratory of Molecular Biology (LMB), UK) and Jonathan K. Watts (University of Massachusetts, USA) |
| title_short | Nucleic acids in chemistry and biology |
| title_sort | nucleic acids in chemistry and biology |
| topic | Nucleinsäuren Nucleic Acids Nucleinsäuren (DE-588)4172117-2 gnd Biochemie (DE-588)4006777-4 gnd |
| topic_facet | Nucleinsäuren Nucleic Acids Biochemie Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=033690073&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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