Preface xvi
Genes Are DNA 1
Introduction 2
DNA Is the Genetic Material of Bacteria 3
DNA Is the Genetic Material of Viruses 4
DNA Is the Genetic Material of Animal Cells 5
Polynucleotide Chains Have Nitrogenous Bases Linked to a Sugar-Phosphate Backbone 6
DNA Is a Double Helix 6
DNA Replication Is Semiconservative 8
DNA Strands Separate at the Replication Fork 9
Genetic Information Can Be Provided by DNA or RNA 10
Nucleic Acids Hybridize by Base Pairing 12
Mutations Change the Sequence of DNA 14
Mutations May Affect Single Base Pairs or Longer Sequences 15
The Effects of Mutations Can Be Reversed 16
Mutations Are Concentrated at Hotspots 17
Many Hotspots Result from Modified Bases 18
Some Hereditary Agents Are Extremely Small 19
Summary 20
Genes Code for Proteins 23
Introduction 24
A Gene Codes for a Single Polypeptide 24
Mutations in the Same Gene Cannot Complement 25
Mutations May Cause Loss-of-Function or Gain-of-Function 26
ALocus May Have Many Different Mutant Alleles 27
A Locus May Have More than One Wild-type Allele 28
Recombination Occurs by Physical Exchange of DNA 28
The Genetic Code Is Triplet 30
Every Sequence Has Three Possible Reading Frames 31
Prokaryotic Genes Are Colinear with Their Proteins 32
Several Processes Are Required to Express the Protein Product of a Gene 33
Proteins Are Trans-acting, but Sites on DNA Are Cis-acting 35
Summary 36
The Interrupted Gene 37
Introduction 38
An Interrupted Gene Consists of Exons and Introns 38
Restriction Endonucleases Are a Key Tool in Mapping DNA 39
Organization of Interrupted Genes May Be Conserved 40
Exon Sequences Are Conserved but Introns Vary 42
Genes Show a Wide Distribution of Sizes 43
Some DNA Sequences Code for More Than One Protein 45
How Did Interrupted Genes Evolve? 47
Some Exons Can Be Equated with Protein Functions 49
The Members of a Gene Family Have a Common Organization 51
Is All Genetic Information Contained in DNA? 53
Summary 53
The Content of the Genome 55
Introduction 56
Genomes Can Be Mapped by Linkage, Restriction Cleavage, or DNA Sequence 56
Individual Genomes Show Extensive Variation 57
RFLPs and SNPs Can Be Used for Genetic Mapping 58
Why Are Genomes So Large? 60
Eukaryotic Genomes Contain Both Nonrepetitive and Repetitive DNA Sequences 61
Genes Can Be Isolated by the Conservation of Exons 63
The Conservation of Genome Organization Helps to Identify Genes 65
Organelles Have DNA 67
Organelle Genomes Are Circular DNAs That Code for Organelle Proteins 69
Mitochondrial DNA Organization Is Variable 70
The Chloroplast Genome Codes for Many Proteins and RNAs 71
Mitochondria Evolved by Endosymbiosis 72
Summary 73
Genome Sequences and Gene Numbers 76
Introduction 77
Bacterial Gene Numbers Range Over an Order of Magnitude 77
Total Gene Number Is Known for Several Eukaryotes 79
How Many Different Types of Genes Are There? 81
The Human Genome Has Fewer Genes Than Expected 83
How Are Genes and Other Sequences Distributed in the Genome? 85
The Y Chromosome Has Several Male-Specific Genes 86
More Complex Species Evolve by Adding New Gene Functions 87
How Many Genes Are Essential? 89
Genes Are Expressed at Widely Differing Levels 92
How Many Genes Are Expressed? 93
Expressed Gene Number Can Be Measured En Masse 93
Summary 94
Clusters and Repeats 98
Introduction 99
Gene Duplication Is a Major Force in Evolution 100
Globin Clusters Are Formed by Duplication and Divergence 101
Sequence Divergence Is the Basis for the Evolutionary Clock 104
The Rate of Neutral Substitution Can Be Measured from Divergence of Repeated Sequences 107
Pseudogenes Are Dead Ends of Evolution 108
Unequal Crossing-over Rearranges Gene Clusters 109
Genes for rRNA Form Tandem Repeats 112
The Repeated Genes for rRNA Maintain Constant Sequence 114
Crossover Fixation Could Maintain Identical Repeats 115
Satellite DNAs Often Lie in Heterochromatin 117
Arthropod Satellites Have Very Short Identical Repeats 119
Mammalian Satellites Consist of Hierarchical Repeats 120
Minisatellites Are Useful for Genetic Mapping 123
Summary 125
Messenger RNA 127
Introduction 128
mRNA Is Produced by Transcription and Is Translated 129
Transfer RNA Forms a Cloverleaf 130
The Acceptor Stem and Anticodon Are at Ends of the Tertiary Structure 131
Messenger RNA Is Translated by Ribosomes 132
Many Ribosomes Bind to One mRNA 133
The Life Cycle of Bacterial Messenger RNA 135
Eukaryotic mRNA Is Modified During or after Its Transcription 137
The 5' End of Eukaryotic mRNA Is Capped 138
The 3' Terminus Is Polyadenylated 139
Bacterial mRNA Degradation Involves Multiple Enzymes 140
mRNA Stability Depends on Its Structure and Sequence 141
mRNA Degradation Involves Multiple Activities 143
Nonsense Mutations Trigger a Surveillance System 144
Eukaryotic RNAs Are Transported 145
mRNA Can Be Specifically Localized 146
Summary 147
Protein Synthesis 151
Introduction 152
Protein Synthesis Occurs by Initiation, Elongation, and Termination 153
Special Mechanisms Control the Accuracy of Protein Synthesis 155
Initiation in Bacteria Needs 30S Subunits and Accessory Factors 157
A Special Initiator tRNA Starts the Polypeptide Chain 158
Use of fMet-tRNA[subscript f] Is Controlled by IF-2 and the Ribosome 150
Initiation Involves Base Pairing Between mRNA and rRNA 161
Small Subunits Scan for Initiation Sites on Eukaryotic mRNA 162
Eukaryotes Use a Complex of Many Initiation Factors 164
Elongation Factor Tu Loads Aminoacyl-tRNA into the A Site 167
The Polypeptide Chain Is Transferred to Aminoacyl-tRNA 168
Translocation Moves the Ribosome 169
Elongation Factors Bind Alternately to the Ribosome 170
Three Codons Terminate Protein Synthesis 172
Termination Codons Are Recognized by Protein Factors 173
Ribosomal RNA Pervades Both Ribosomat Subunits 175
Ribosomes Have Several Active Centers 177
16S rRNA Plays an Active Role in Protein Synthesis 179
23S rRNA Has Peptidyl Transferase Activity 182
Ribosomal Structures Change When the Subunits Come Together 183
Summary 183
Using the Genetic Code 189
Introduction 190
Related Codons Represent Related Amino Acids 190
Codon-Anticodon Recognition Involves Wobbling 192
tRNAs Are Processed from Longer Precursors 194
tRNA Contains Modified Bases 194
Modified Bases Affect Anticodon-Codon Pairing 196
There Are Sporadic Alterations of the Universal Code 197
Novel Amino Acids Can Be Inserted at Certain Stop Codons 199
tRNAs Are Charged with Amino Acids by Synthetases 200
Aminoacyl-tRNA Synthetases Fall into Two Groups 201
Synthetases Use Proofreading to Improve Accuracy 203
Suppressor tRNAs Have Mutated Anticodons That Read New Codons 206
There Are Nonsense Suppressors for Each Termination Codon 207
Suppressors May Compete with Wild-Type Reading of the Code 208
The Ribosome Influences the Accuracy of Translation 209
Recoding Changes Codon Meanings 211
Frameshifting Occurs at Slippery Sequences 213
Bypassing Involves Ribosome Movement 214
Summary 215
Protein Localization 218
Introduction 220
Passage Across a Membrane Requires a Special Apparatus 220
Protein Translocation May Be Posttranslational or Cotranslational 221
Chaperones May Be Required for Protein Folding 223
Chaperones Are Needed by Newly Synthesized and by Denatured Proteins 224
The Hsp70 Family Is Ubiquitous 226
Signal Sequences Initiate Translocation 227
The Signal Sequence Interacts with the SRP 228
The SRP Interacts with the SRP Receptor 229
The Translocon Forms a Pore 231
Translocation Requires Insertion into the Translocon and (Sometimes) a Ratchet in the ER 233
Reverse Translocation Sends Proteins to the Cytosol for Degradation 234
Proteins Reside in Membranes by Means of Hydrophobic Regions 235
Anchor Sequences Determine Protein Orientation 236
How Do Proteins Insert into Membranes? 238
Posttranslational Membrane Insertion Depends on Leader Sequences 240
A Hierarchy of Sequences Determines Location within Organelles 241
Inner and Outer Mitochondrial Membranes Have Different Translocons 243
Peroxisomes Employ Another Type of Translocation System 245
Bacteria Use Both Cotranslational and Posttranslational Translocation 246
The Sec System Transports Proteins into and Through the Inner Membrane 247
Sec-Independent Translocation Systems in E. coli 249
Summary 250
Transcription 256
Introduction 258
Transcription Occurs by Base Pairing in a "Bubble" of Unpaired DNA 259
The Transcription Reaction Has Three Stages 260
Phage T7 RNA Polymerase Is a Useful Model System 251
A Model for Enzyme Movement Is Suggested by the Crystal Structure 262
Bacterial RNA Polymerase Consists of Multiple Subunits 265
RNA Polymerase Consists of the Core Enzyme and Sigma Factor 267
The Association with Sigma Factor Changes at Initiation 267
A Stalled RNA Polymerase Can Restart 269
How Does RNA Polymerase Find Promoter Sequences? 270
Sigma Factor Controls Binding to DNA 271
Promoter Recognition Depends on Consensus Sequences 272
Promoter Efficiencies Can Be Increased or Decreased by Mutation 274
RNA Polymerase Binds to One Face of DNA 275
Supercoiling Is an Important Feature of Transcription 277
Substitution of Sigma Factors May Control Initiation 278
Sigma Factors Directly Contact DNA 280
Sigma Factors May Be Organized into Cascades 282
Sporulation Is Controlled by Sigma Factors 283
Bacterial RNA Polymerase Terminates at Discrete Sites 286
There Are Two Types of Terminators in E. coli 287
How Does Rho Factor Work? 288
Antitermination Is a Regulatory Event 291
Antitermination Requires Sites That Are Independent of the Terminators 292
Termination and Antitermination Factors Interact with RNA Polymerase 293
Summary 295
The Operon 300
Introduction 302
Regulation Can Be Negative or Positive 303
Structural Gene Clusters Are Coordinately Controlled 304
The lac Genes Are Controlled by a Repressor 304
The lac Operon Can Be Induced 305
Repressor Is Controlled by a Small-Molecule Inducer 306
cis-Acting Constitutive Mutations Identify the Operator 308
trans-Acting Mutations Identify the Regulator Gene 309
Multimeric Proteins Have Special Genetic Properties 309
The Repressor Monomer Has Several Domains 310
Repressor Is a Tetramer Made of Two Dimers 311
DNA-Binding Is Regulated by an Allosteric Change in Conformation 312
Mutant Phenotypes Correlate with the Domain Structure 312
Repressor Protein Binds to the Operator 313
Binding of Inducer Releases Repressor from the Operator 314
Repressor Binds to Three Operators and Interacts with RNA Polymerase 315
Repressor Is Always Bound to DNA 316
The Operator Competes with Low-Affinity Sites to Bind Repressor 317
Repression Can Occur at Multiple Loci 319
Cyclic AMP Is an Effector That Activates CRP to Act at Many Operons 320
CRP Functions in Different Ways in Different Target Operons 321
Translation Can Be Regulated 323
r-Protein Synthesis Is Controlled by Autogenous Regulation 325
Phage T4 p32 Is Controlled by an Autogenous Circuit 326
Autogenous Regulation Is Often Used to Control Synthesis of Macromolecular Assemblies 327
Summary 328
Regulatory RNA 331
Introduction 332
Alternative Secondary Structures Control Attenuation 333
Termination of Bacillus subtilis trp Genes Is Controlled by Tryptophan and by tRNA[superscript Trp] 333
The Escherichia coli tryptophan Operon Is Controlled by Attenuation 335
Attenuation Can Be Controlled by Translation 336
Antisense RNA Can Be Used to Inactivate Gene Expression 338
Small RNA Molecules Can Regulate Translation 339
Bacteria Contain Regulator RNAs 341
MicroRNAs Are Regulators in Many Eukaryotes 342
RNA Interference Is Related to Gene Silencing 343
Summary 345
Phage Strategies 349
Introduction 350
Lytic Development Is Divided into Two Periods 352
Lytic Development Is Controlled by a Cascade 353
Two Types of Regulatory Event Control the Lytic Cascade 354
The T7 and T4 Genomes Show Functional Clustering 355
Lambda Immediate Early and Delayed Early Genes Are Needed for Both Lysogeny and the Lytic Cycle 356
The Lytic Cycle Depends on Antitermination 357
Lysogeny Is Maintained by Repressor Protein 359
The Repressor and Its Operators Define the Immunity Region 360
The DNA-Binding Form of Repressor Is a Dimer 361
Repressor Uses a Helix-Turn-Helix Motif to Bind DNA 362
The Recognition Helix Determines Specificity for DNA 363
Repressor Dimers Bind Cooperatively to the Operator 364
Repressor at 0[subscript R]2 Interacts with RNA Polymerase at P[subscript RM] 365
Repressor Maintains an Autogenous Circuit 366
Cooperative Interactions Increase the Sensitivity of Regulation 367
The cII and cIII Genes Are Needed to Establish Lysogeny 368
A Poor Promoter Requires cII Protein 369
Lysogeny Requires Several Events 369
The cro Repressor Is Needed for Lytic Infection 371
What Determines the Balance Between Lysogeny and the Lytic Cycle? 373
Summary 374
The Replicon 376
Introduction 377
Replicons Can Be Linear or Circular 378
Origins Can Be Mapped by Autoradiography and Electrophoresis 379
Does Methylation at the Origin Regulate Initiation? 380
Origins May Be Sequestered after Replication 381
Each Eukaryotic Chromosome Contains Many Replicons 383
Replication Origins Can Be Isolated in Yeast 384
Licensing Factor Controls Eukaryotic Rereplication 385
Licensing Factor Consists of MCM Proteins 386
D Loops Maintain Mitochondrial Origins 388
Summary 389
Extrachromosomal Replicons 392
Introduction 393
The Ends of Linear DNA Are a Problem for Replication 393
Terminal Proteins Enable Initiation at the Ends of Viral DNAs 394
Rolling Circles Produce Multimers of a Replicon 396
Rolling Circles Are Used to Replicate Phage Genomes 397
The F Plasmid Is Transferred by Conjugation between Bacteria 398
Conjugation Transfers Single-Stranded DNA 400
The Bacterial Ti Plasmid Causes Crown Gall Disease in Plants 401
T-DNA Carries Genes Required for Infection 402
Transfer of T-DNA Resembles Bacterial Conjugation 405
Summary 407
Bacterial Replication Is Connected to the Cell Cycle 408
Introduction 409
Replication Is Connected to the Cell Cycle 410
The Septum Divides a Bacterium into Progeny That Each Contain a Chromosome 411
Mutations in Division or Segregation Affect Cell Shape 412
FtsZ Is Necessary for Septum Formation 413
min Genes Regulate the Location of the Septum 415
Chromosomal Segregation May Require Site-Specific Recombination 415
Partitioning Involves Separation of the Chromosomes 417
Single-Copy Plasmids Have a Partitioning System 419
Plasmid Incompatibility Is Determined by the Replicon 421
The ColE1 Compatibility System Is Controlled by an RNA Regulator 422
How Do Mitochondria Replicate and Segregate? 424
Summary 425
DNA Replication 428
Introduction 429
DNA Polymerases Are the Enzymes That Make DNA 430
DNA Polymerases Have Various Nuclease Activities 431
DNA Polymerases Control the Fidelity of Replication 432
DNA Polymerases Have a Common Structure 433
DNA Synthesis Is Semidiscontinuous 434
The [phi]X Model System Shows How Single-Stranded DNA Is Generated for Replication 435
Priming Is Required to Start DNA Synthesis 437
DNA Polymerase Holoenzyme Has Three Subcomplexes 439
The Clamp Controls Association of Core Enzyme with DNA 440
Coordinating Synthesis of the Lagging and Leading Strands 442
Okazaki Fragments Are Linked by Ligase 443
Separate Eukaryotic DNA Polymerases Undertake Initiation and Elongation 444
Phage T4 Provides Its Own Replication Apparatus 445
Creating the Replication Forks at an Origin 448
Common Events in Priming Replication at the Origin 450
The Primosome Is Needed to Restart Replication 451
Summary 453
Homologous and Site-Specific Recombination 457
Introduction 459
Homologous Recombination Occurs between Synapsed Chromosomes 460
Breakage and Reunion Involves Heteroduplex DNA 462
Double-Strand Breaks Initiate Recombination 464
Recombining Chromosomes Are Connected by the Synaptonemal Complex 465
The Synaptonemal Complex Forms after Double-Strand Breaks 467
Pairing and Synaptonemal Complex Formation Are Independent 469
The Bacterial RecBCD System Is stimulated by chi Sequences 470
Strand-Transfer Proteins Catalyze Single-Strand Assimilation 471
The Ruv System Resolves Holliday Junctions 473
Gene Conversion Accounts for Interallelic Recombination 475
Supercoiling Affects the Structure of DNA 476
Topoisomerases Relax or Introduce Supercoils in DNA 478
Topoisomerases Break and Reseal Strands 480
Gyrase Functions by Coil Inversion 481
Specialized Recombination Involves Specific Sites 482
Site-Specific Recombination Involves Breakage and Reunion 484
Site-Specific Recombination Resembles Topoisomerase Activity 484
Lambda Recombination Occurs in an Intasome 486
Yeast Can Switch Silent and Active Loci for Mating Type 488
The MAT Locus Codes for Regulator Proteins 490
Silent Cassettes at HML and HMR Are Repressed 492
Unidirectional Transposition Is Initiated by the Recipient MAT Locus 493
Regulation of HO Expression Controls Switching 494
Summary 496
Repair Systems 499
Introduction 500
Repair Systems Correct Damage to DNA 502
Excision Repair Systems in E. coli 503
Excision-Repair Pathways in Mammalian Cells 504
Base Flipping Is Used by Methylases and Glycosylases 506
Error-Prone Repair and Mutator Phenotypes 507
Controlling the Direction of Mismatch Repair 507
Recombination-Repair Systems in E. coli 510
Recombination Is an Important Mechanism to Recover from Replication Errors 511
RecA Triggers the SOS System 513
Eukaryotic Cells Have Conserved Repair Systems 515
A Common System Repairs Double-Strand Breaks 516
Summary 518
Transposons 521
Introduction 522
Insertion Sequences Are Simple Transposition Modules 524
Composite Transposons Have IS Modules 525
Transposition Occurs by Both Replicative and Nonreplicative Mechanisms 527
Transposons Cause Rearrangement of DNA 528
Common Intermediates for Transposition 530
Replicative Transposition Proceeds through a Cointegrate 531
Nonreplicative Transposition Proceeds by Breakage and Reunion 533
TnA Transposition Requires Transposase and Resolvase 534
Transposition of Tn10 Has Multiple Controls 536
Controlling Elements in Maize Cause Breakage and Rearrangements 538
Controlling Elements Form Families of Transposons 540
Spm Elements Influence Gene Expression 542
The Role of Transposable Elements in Hybrid Dysgenesis 544
P Elements Are Activated in the Germline 545
Summary 546
Retroviruses and Retroposons 550
Introduction 551
The Retrovirus Life Cycle Involves Transposition-Like Events 551
Retroviral Genes Code for Polyproteins 552
Viral DNA Is Generated by Reverse Transcription 554
Viral DNA Integrates into the Chromosome 556
Retroviruses May Transduce Cellular Sequences 558
Yeast Ty Elements Resemble Retroviruses 559
Many Transposable Elements Reside in Drosophila melanogaster 561
Retroposons Fall into Three Classes 562
The Alu Family Has Many Widely Dispersed Members 564
Processed Pseudogenes Originated as Substrates for Transposition 565
LINES Use an Endonuclease to Generate a Priming End 566
Summary 567
Immune Diversity 570
Introduction 572
Clonal Selection Amplifies Lymphocytes That Respond to Individual Antigens 574
Immunoglobulin Genes Are Assembled from Their Parts in Lymphocytes 575
Light Chains Are Assembled by a Single Recombination 577
Heavy Chains Are Assembled by Two Recombinations 579
Recombination Generates Extensive Diversity 580
Immune Recombination Uses Two Types of Consensus Sequence 581
Recombination Generates Deletions or Inversions 582
Allelic Exclusion Is Triggered by Productive Rearrangement 582
The RAG Proteins Catalyze Breakage and Reunion 584
Early Heavy Chain Expression Can Be Changed by RNA Processing 586
Class Switching Is Caused by DNA Recombination 587
Switching Occurs by a Novel Recombination Reaction 589
Somatic Mutation Generates Additional Diversity in Mouse and Human Being 590
Somatic Mutation Is Induced by Cytidine Deaminase and Uracil Glycosylase 591
Avian Immunoglobulins Are Assembled from Pseudogenes 593
B Cell Memory Allows a Rapid Secondary Response 594
T Cell Receptors Are Related to Immunoglobulins 595
The T Cell Receptor Functions in Conjunction with the MHC 597
The Major Histocompatibility Locus Codes for Many Genes of the Immune System 599
Innate Immunity Utilizes Conserved Signaling Pathways 602
Summary 604
Promoters and Enhancers 609
Introduction 610
Eukaryotic RNA Polymerases Consist of Many Subunits 612
Promoter Elements Are Defined by Mutations and Footprinting 613
RNA Polymerase I Has a Bipartite Promoter 614
RNA Polymerase III Uses Both Downstream and Upstream Promoters 615
TF[subscript III]B Is the Commitment Factor for Pol III Promoters 616
The Startpoint for RNA Polymerase II 618
TBP Is a Universal Factor 619
TBP Binds DNA in an Unusual Way 620
The Basal Apparatus Assembles at the Promoter 621
Initiation Is Followed by Promoter Clearance 623
A Connection between Transcription and Repair 625
Short Sequence Elements Bind Activators 627
Promoter Construction Is Flexible but Context Can Be Important 628
Enhancers Contain Bidirectional Elements That Assist Initiation 629
Enhancers Contain the Same Elements That Are Found at Promoters 630
Enhancers Work by Increasing the Concentration of Activators Near the Promoter 631
Gene Expression Is Associated with Demethylation 632
CpG Islands Are Regulatory Targets 634
Summary 635
Activating Transcription 640
Introduction 641
There Are Several Types of Transcription Factors 642
Independent Domains Bind DNA and Activate Transcription 643
The Two Hybrid Assay Detects Protein-Protein Interactions 645
Activators Interact with the Basal Apparatus 646
Some Promoter-Binding Proteins Are Repressors 648
Response Elements Are Recognized by Activators 649
There Are Many Types of DNA-Binding Domains 651
A Zinc Finger Motif Is a DNA-Binding Domain 652
Steroid Receptors Are Activators 653
Steroid Receptors Have Zinc Fingers 655
Binding to the Response Element Is Activated by Ligand-Binding 656
Steroid Receptors Recognize Response Elements by a Combinatorial Code 657
Homeodomains Bind Related Targets in DNA 658
Helix-Loop-Helix Proteins Interact by Combinatorial Association 660
Leucine Zippers Are Involved in Dimer Formation 662
Summary 663
RNA Splicing and Processing 667
Introduction 669
Nuclear Splice Junctions Are Short Sequences 670
Splice Junctions Are Read in Pairs 671
Pre-mRNA Splicing Proceeds through a Lariat 673
snRNAs Are Required for Splicing 674
U1 snRNP Initiates Splicing 676
The E Complex Can Be Formed by Intron Definition or Exon Definition 678
5 snRNPs Form the Spliceosome 679
An Alternative Splicing Apparatus Uses Different snRNPs 681
Splicing Is Connected to Export of mRNA 682
Group II Introns Autosplice via Lariat Formation 683
Alternative Splicing Involves Differential Use of Splice Junctions 685
trans-Splicing Reactions Use Small RNAs 688
Yeast tRNA Splicing Involves Cutting and Rejoining 690
The Splicing Endonuclease Recognizes tRNA 691
tRNA Cleavage and Ligation Are Separate Reactions 692
The Unfolded Protein Response Is Related to tRNA Splicing 693
The 3' Ends of polI and polIII Transcripts Are Generated by Termination 694
The 3' Ends of mRNAs Are Generated by Cleavage and Polyadenylation 695
Cleavage of the 3' End of Histone mRNA May Require a Small RNA 697
Production of rRNA Requires Cleavage Events 697
Small RNAs Are Required for rRNA Processing 699
Summary 700
Catalytic RNA 706
Introduction 707
Group I Introns Undertake Self-Splicing by Transesterification 707
Group I Introns Form a Characteristic Secondary Structure 709
Ribozymes Have Various Catalytic Activities 711
Some Group I Introns Code for Endonucleases That Sponsor Mobility 715
Group II Introns May Code for Multifunction Proteins 716
Some Autosplicing Introns Require Maturases 717
The Catalytic Activity of RNAase P Is Due to RNA 718
Viroids Have Catalytic Activity 718
RNA Editing Occurs at Individual Bases 720
RNA Editing Can Be Directed by Guide RNAs 721
Protein Splicing Is Autocatalytic 724
Summary 725
Chromosomes 729
Introduction 730
Viral Genomes Are Packaged into Their Coats 731
The Bacterial Genome Is a Nucleoid 734
The Bacterial Genome Is Supercoiled 735
Eukaryotic DNA Has Loops and Domains Attached to a Scaffold 736
Specific Sequences Attach DNA to an Interphase Matrix 737
Chromatin Is Divided into Euchromatin and Heterochromatin 738
Chromosomes Have Banding Patterns 740
Lampbrush Chromosomes Are Extended 741
Polytene Chromosomes Form Bands 742
Polytene Chromosomes Expand at Sites of Gene Expression 743
The Eukaryotic Chromosome Is a Segregation Device 744
Centromeres May Contain Repetitive DNA 746
Centromeres Have Short DNA Sequences in S. cerevisiae 747
The Centromere Binds a Protein Complex 748
Telomeres Have Simple Repeating Sequences 748
Telomeres Seat the Chromosome Ends 749
Telomeres Are Synthesized by a Ribonucleoprotein Enzyme 750
Telomeres Are Essential for Survival 752
Summary 753
Nucleosomes 757
Introduction 758
The Nucleosome Is the Subunit of All Chromatin 759
DNA Is Coiled in Arrays of Nucleosomes 761
Nucleosomes Have a Common Structure 762
DNA Structure Varies on the Nucleosomal Surface 763
The Periodicity of DNA Changes on the Nucleosome 766
Organization of the Histone Octamer 767
The Path of Nucleosomes in the Chromatin Fiber 769
Reproduction of Chromatin Requires Assembly of Nucleosomes 771
Do Nucleosomes Lie at Specific Positions? 774
Are Transcribed Genes Organized in Nucleosomes? 777
Histone Octamers Are Displaced by Transcription 779
Nucleosome Displacement and Reassembly Require Special Factors 781
Insulators Block the Actions of Enhancers and Heterochromatin 781
Insulators Can Define a Domain 783
Insulators May Act in One Direction 784
Insulators Can Vary in Strength 785
DNAase Hypersensitive Sites Reflect Changes in Chromatin Structure 786
Domains Define Regions That Contain Active Genes 788
An LCR May Control a Domain 789
What Constitutes a Regulatory Domain? 790
Summary 791
Controlling Chromatin Structure 796
Introduction 797
Chromatin Can Have Alternative States 797
Chromatin Remodeling Is an Active Process 798
Nucleosome Organization May Be Changed at the Promoter 801
Histone Modification Is a Key Event 802
Histone Acetylation Occurs in Two Circumstances 805
Acetylases Are Associated with Activators 806
Deacetylases Are Associated with Repressors 808
Methylation of Histones and DNA Is Connected 808
Chromatin States Are Interconverted by Modification 809
Promoter Activation Involves an Ordered Series of Events 809
Histone Phosphorylation Affects Chromatin Structure 810
Some Common Motifs Are Found in Proteins That Modify Chromatin 811
Summary 812
Epigenetic Effects Are Inherited 818
Introduction 819
Heterochromatin Propagates from a Nucleation Event 820
Heterochromatin Depends on Interactions with Histones 822
Polycomb and Trithorax Are Antagonistic Repressors and Activators 824
X Chromosomes Undergo Global Changes 826
Chromosome Condensation Is Caused by Condensins 828
DNA Methylation Is Perpetuated by a Maintenance Methylase 830
DNA Methylation Is Responsible for Imprinting 832
Oppositely Imprinted Genes Can Be Controlled by a Single Center 834
Epigenetic Effects Can Be Inherited 835
Yeast Prions Show Unusual Inheritance 836
Prions Cause Diseases in Mammals 839
Summary 840
Glossary 845
Index 867
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