Genome Duplication

Contents in Detail

Chapter 1 Genomes 1 

Genome Composition 2

DNA 2

Composition Of DNA 3

DNA Structure 4

Primary Structure 4

Secondary Structure 5

Tertiary Structure 9

Superhelicity 10

Superhelicity Generated By Nucleosome Assembly 11

Superhelicity Generated By DNA Gyrases 11

Superhelicity Generated By Transcription 12

Superhelicity Generated By Replication 12

Noncanonical DNA Structures 13

Z-DNA 13

Cruciform DNA 13

Triplex DNA 15

Quadruplex DNA 17

Slipped-Strand DNA 19

Genome Characteristics 19

Chromosome Shape, Number, And Distribution 19

DNA Length 20

C-Value Paradox 20

Genetic Complexity Paradox 22

Summary 23

Additional Reading 25

Literature Cited 25

Chapter 2 Three Domains of Life 27

In the Beginning … 27

Prebiotic Era 28

Cellular Life 30

Phylogenetics 30

Characteristics of the Three Domains 33

Bacteria 34

Archaea 34

Eukaryotes 35

Viruses: Ubiquitous Parasites 37
Summary 37

Additional Reading 37

Chapter 3 Replication Forks 39

DNA Replication 39

Semi-Conservative DNA Replication 40

DNA Replication And Natural Selection 42

DNA Replication Forks 43

The Replication-Fork Paradox 43

Sequence of Events at Replication Forks 46

DNA Unwinding And Leading-Strand Synthesis 47

DNA Relaxation 49

Lagging-Strand Synthesis 50

Conservation Of Replication-Fork Events 53

Organization of Replication Forks 54

Replication-Fork Configuration 54

Replication-Fork Factories 56

Replication-Fork Velocity 58
Nucleotide Pools 59
Summary 61

Additional Reading 62

Literature Cited 62

Chapter 4 Replication Proteins: Leading-Strand Synthesis 63

DNA Helicases 63

The DnaB Family Of Helicases 65

The MCM Family Of Helicases 66

Rotary Engine Activity Of DNA Helicases 67

How Helicases Unwind DNA 68

Single-Strand-Specific DNA-Binding Proteins70
DNA Polymerases 73

The DNA Polymerase I Paradigm 74

DNA Polymerase Families 76

DNA Polymerase Fidelity And Molecular Evolution 83

Sliding Clamps 84

Bacteria 84

Archaea And Eukarya 85

DNA Topoisomerases 85

Type IA Enzymes 86

Type IB Enzymes 87

Type II Enzymes 88

Summary 90

Additional Reading 91

Literature Cited 92

Chapter 5 Replication Proteins: Laggin-Strand Synthesis 93

RNA-Primed Nascent DNA 93
DNA Primase 96XI
Initiation of Okazaki-Fragment Synthesis 98
The Helicase-Primase Paradox 99

Bacteria 100

Archaea And Eukarya100

Handp-off From Primase to Polymerase 101

Bacteria 101

Eukarya 102

Hand-Off From Iniator Polymerase to Replicator Polymerase 102
Sliding Clamp Loaders 103

Bacteria 103

Archaea And Eukarya 104

Primer Excision 105

Bacteria 105Eukarya 106

DNA Ligation 107
THE Ringmaster 109
Dynamic Processivity 111
Summary 114

Additional Reading 115

Chapter 6 Termination 117

Replication-Fork Termination 117

When Forks Collide 117

Topological Problems Unique To Replication-Fork Termination 118

Replication-Fork Barriers 120

Replication-Fork Barriers In Bacteria 120

Replication-Fork Barriers In Eukarya 124

Other Impediments to Replication Forks 126
The Role of Replication-Fork Barriers in Nature 127
The Termination Paradox 127

Protein-Nucleotide Primers 128

Circularization 128

Concatemer Formation 128

Telomeres And Telomerase 128

Summary 133

Additional Reading 134

Chapter 7 Chromatin Assembly, Cohesion, and Modification 135

Chromatin 136

Bacteria 136

Archaea 140

Eukarya 142

Eukaryotic Chromatin and DNA Replication 147

Replication Origins 147

Replication Forks 148

Sister Chromatid Cohesion 154

Formation Of A Cohesin Ring Around Sister Chromatids 155

Establishment Of Cohesion Between Sister Chromatids 157

Dissolution Of Cohesion Between Sister Chromatids 158

Duplication of Epigenetic Information 159

Nucleosome Segregation and Positioning 159

Protein Modification 161

DNA Methylation 163

Summary 166

Additional Reading 167

Literature Cited 167

Chapter 8 Replicons 169

The Replicon Model 169

The Classical Replicon Model 169

The Replicon Model Today 170

Visualizing Replicons 171

Why Replicons? 174

Replicon Taxonomy 175

DNA Structure And Replicator Location 175

Modes Of DNA Replication 176

Modes Of DNA Synthesis 176

Six Manifestations of the Replicon 178

A. dsDNA With Internal Replicators That Use Replication Forks 178

B. dsDNA With Internal Replicators That Use Single-Strand Displacement 179

C. dsDNA With Internal Replicators That Use The Rolling Circle 181

D. dsDNA With Terminal Replicators That Use Single-Strand Displacement And Then Gap-Filling 182

E. ssDNA With Internal Replicators That Use Gap-Filling And Then Single-Strand Displacement 183

F. ssDNA With Terminal Replicators That Use Gap-Filling And Then Single-Strand Displacement 185

Summary 188

Additional Reading 189

Literature Cited 189

Chapter 9 Replication Origins 191

Patterns of Initiation 192
Finding Replication Origins 193

Replicator Activity 193

Origins Of Bidirectional Replication 194

Nascent-Strand Abundance 194xii CONTENTS IN DETAIL 

DNA Sequence Duplication 194

Leading-Strand Sequence Bias 195

Characteristics of Replication Origins 195

Origin Anatomy 195

Origin Specificity 197

Origin Function 197

Origin Density 202

Origin Usage 204

Origin Timing 205

Developmental Acquisition of Site-Specificity 206
Paradoxes and Solutions 207

The Replicator Paradox 207

The Site-Selection Paradox 213

The MCM Paradox 215

Summary 218

Additional Reading 221

Literature Cited 222

Chapter 10 Origin Paradigms 223

DNA-Nicking Mechanism 223
Protein-Priming Mechanism 224
DNA Transcription Mechanism 227

Bacteriophage T7 227

Bacteriophage T4 229

Bacterial Plasmid ColE1 229

Mitochondrial DNA 230

DNA Helicase Mechanism 232

Simian Virus 40 232

Polyomavirus 234

Papillomavirus 234

Herpes Simplex Virus 234

DNA Helicase Loader Mechanism 235

Bacteria 236

Archaea 240

Single-Cell Eukarya 242

Multicellular Eukarya 246

Why DNA Helicase Loaders? 254

Amplification Origins 255

Sciara coprophila 255

Drosophila melanogaster 255

Tetrahymena thermophila 258

Summary 259

Chapter 11 Initiation 261

The Road to Replication Forks 262

Replication-Fork Assembly And Cell Proliferation 264

Where The Road Splits 266

Viral Genomes 267
Bacterial Genomes 269

preRC Assembly On Bacterial Genomes 270

preIC Assembly On Bacterial Genomes 272

Archaeal Genomes 273
Eukaryal Genomes 275

preRC Assembly (Origin Licensing) On Eukaryotic Genomes 275

preIC Assembly On Eukaryotic Genomes 281

Summary 285

Additional Reading 286

Literature Cited 286

Chapter 12 Cell Cycles 287

The Bacterial Cell Cycle 287

The Initiator/Replicator Ratio Triggers Genome Duplication 289

Suppression of Reinitiation Within A Single Cell Cycle 290

The Archaeal Cell Cycle 293
The Eukaryotic Mitotic Cell Cycle 293

Common Features 293

Abbreviated Mitotic Cell Cycles 295

Cell-Cycle Analysis 295

Accelerators And Brakes 298

Yin And Yang 301

Genome Duplication Preceds Cell Division 302

Driving the G2ÆM Transition 303

Regulating preRC Assembly 304

Driving The MÆG1 Transition 305

Driving The G1ÆS Transition 307

Preventing DNA Re-Replication 309

Single-Cell Eukarya 310

Multicellular Eukarya 311

Parallel Pathways 315
Functional Redundancy 316
Developmentally Programmed Polyploidy 316

Initiating Endocycles 318

Sustaining Endocycles 321

Two APCs, Two Cell Cycles 322

Summary 322

Additional Reading 324

Chapter 13 Checkpoints 325

Restriction Checkpoint 328

Bacteria 328

Archaea 330

Eukarya 330xiii CONTENTS IN DETAIL 

DNA Damage Response 335

The SOS Response In Bacteria 337

Restarting Replication Forks In Bacteria 340

Archaea 346

Eukarya 346

G1 DNA Damage Checkpoint 349

DNA-Replication Checkpoint 350

G2 DNA Damage Checkpoint 353

The Eukaryotic Replisome Revisited 354

Stabilization Of Replication Forks 355

Mediators 357

Replication-Fork Restart In Eukarya 357

G2 Checkpoint 358

Bacteria 359

ukarya 359

Spindle-Assembly Checkpoint 360

Mitotic Cells 360

Meiotic Cells 362

Summary 364

Additional Reading 366

Literature Cited 366

Chapter 14 Human Disease 367

Infectious Diseases 368

Viruses 368

Bacteria 373

Archaea 373

Noninfectious Diseases 374

The Road To Cancer 374

DNA Replication Proteins As Cancer Biomarkers 380

Heritable Diseases 382

The ‘Seven Deadly Sins’ Of DNA Replication 382

The Road To Nucleotide-Repeat Disorders 384

Mutations In DNA Replication Genes 389

Pharmacological Agents That Target DNA Replication 391

Antiviral Pharmaceuticals 391

Antibiotic Pharmaceuticals 396

Anti-Cancer Pharmaceuticals 397

Summary 406

Additional Reading Literature Cited 408 

Chapter 15 Evolution of Cellular Replication Machines 409

Replication Machines in Bacteria, Archaea, and Eukarya 409
Making the Jump from RNA to DNA Genomes 411
A Role of Viruses in the Evolution of DNA Genomes? 412
Did DNA Evolve in Viruses as a Way to Evade Host Defenses? 412
Replicon Takeover 414
The Acquisition of Multiple Replication Origins 415
Viruses as a Fossil Record 416
Summary 416

Additional Reading 417

Glossary 418

Index 425E 408