Preface XVII
Authors XIX
1 Introduction 1
1.1 Historical Aspects 1
1.2 Yeast as a Eukaryotic Model System 1
Further Reading 3
2 Yeast Cell Architecture and Functions 5
2.1 General Morphology 5
2.2 Cell Envelope 6
2.2.1 Cell Wall 7
2.2.2 Plasma Membrane 8
2.3 Cytoplasm and Cytoskeleton 8
2.3.1 Yeast Cytoplasm 8
2.3.2 Yeast Cytoskeleton 9
2.4 Yeast Nucleus 14
2.4.1 Overview 14
2.4.2 Nuclear Pore 14
2.4.3 Yeast Chromosomes 17
2.5 Organellar Compartments 17
2.5.1 ER and the Golgi Apparatus 18
2.5.2 Transport Vesicles 18
2.5.3 Vacuolar System 20
2.5.4 Endocytosis and Exocytosis 21
2.5.5 Mitochondria 21
2.5.6 Peroxisomes 22
Further Reading 23
3 Yeast Metabolism 25
3.1 Metabolic Pathways and Energy 25
3.2 Catabolism of Hexose Carbon Sources 25
3.2.1 Principal Pathways 25
3.2.2 Respiration Versus Fermentation 26
3.2.3 Catabolism of Other Sugars – Galactose 27
3.2.4 Metabolism of Non-Hexose Carbon Sources 28
3.3 Gluconeogenesis and Carbohydrate Biosynthesis 30
3.3.1 Gluconeogenesis 30
3.3.2 Storage Carbohydrates 30
3.3.3 Unusual Carbohydrates 31
3.3.4 Structural Carbohydrates 34
3.4 Fatty Acid and Lipid Metabolism 35
3.4.1 Fatty Acids 35
3.4.2 Lipids 35
3.4.3 Glycolipids 36
3.4.4 Isoprenoid Biosynthesis 40
3.5 Nitrogen Metabolism 42
3.5.1 Catabolic Pathways 42
3.5.2 Amino Acid Biosynthesis Pathways 44
3.6 Nucleotide Metabolism 48
3.6.1 Pyrimidine Derivatives 48
3.6.2 Purine Derivatives 48
3.6.3 Deoxyribonucleotides 50
3.6.4 Nucleotide Modification 50
3.7 Phosphorus and Sulfur Metabolism 51
3.7.1 Phosphate 51
3.7.2 Sulfur 52
3.8 Vitamins and Cofactors 53
3.8.1 Biotin 53
3.8.2 Thiamine 53
3.8.3 Pyridoxine 54
3.8.4 NAD 54
3.8.5 Riboflavin Derivatives 54
3.8.6 Pantothenic Acid and Coenzyme A 55
3.8.7 Folate 55
3.8.8 Tetrapyrroles 55
3.8.9 Ubiquinone (Coenzyme Q) 56
3.9 Transition Metals 57
Further Reading 58
4 Yeast Molecular Techniques 59
4.1 Handling of Yeast Cells 59
4.1.1 Growth of Yeast Cells 59
4.1.2 Isolation of Particular Cell Types and Components 59
4.2 Genetic Engineering and Reverse Genetics 59
4.2.1 Molecular Revolution 59
4.2.2 Transformation of Yeast Cells 61
4.2.3 Yeast Cosmid Vectors 64
4.2.4 Yeast Artificial Chromosomes 65
4.3 More Genetic Tools from Yeast Cells 65
4.3.1 Yeast Two-Hybrid System 65
4.3.2 Yeast Three-Hybrid System 66
4.3.3 Yeast One-Hybrid (Matchmaker) System 67
4.4 Techniques in Yeast Genome Analyses 67
4.4.1 Microarrays 67
4.4.2 Affinity Purification 70
4.4.3 Mass Spectrometry 70
Further Reading 72
5 Yeast Genetic Structures and Functions 73
5.1 Yeast Chromosome Structure and Function 73
5.1.1 Yeast Chromatin 73
5.1.2 Centromeres 85
5.1.3 Replication Origins and Replication 85
5.1.4 Telomeres 96
5.1.5 Transposons in Yeast 98
5.2 Yeast tRNAs, Genes, and Processing 103
5.2.1 Yeast tRNAs 103
5.2.2 Current Status of Yeast tRNA Research 106
5.3 Yeast Ribosomes: Components, Genes, and Maturation 113
5.3.1 Historical Overview 113
5.3.2 Ribosomal Components 113
5.3.3 Components and Pathways of Yeast Ribosome Maturation 114
5.4 Messenger RNAs 116
5.4.1 First Approaches to the Structure of Yeast mRNAs 116
5.4.2 Introns and Processing of pre-mRNA 117
5.4.3 Provenance of Introns 121
5.5 Extrachromosomal Elements 121
5.5.1 Two Micron DNA 121
5.5.2 Killer Plasmids 121
5.5.3 Yeast Prions 121
5.6 Yeast Mitochondrial Genome 123
Further Reading 125
6 Gene Families Involved in Cellular Dynamics 127
6.1 ATP- and GTP-Binding Proteins 127
6.1.1 ATPases 127
6.1.2 Small GTPases and Their Associates 133
6.1.3 G-Proteins 136
6.2 Regulatory ATPases: AAA and AAAþ Proteins 138
6.2.1 ATP-Dependent Proteases 138
6.2.2 Membrane Fusion Proteins 139
6.2.3 Cdc48 139
6.2.4 Peroxisomal AAA Proteins 139
6.2.5 Katanin and Vps4p 139
6.2.6 Dynein 139
6.2.7 DNA Replication Proteins 140
6.2.8 RuvB-Like Proteins 140
6.2.9 Other AAAþ Yeast Proteins 140
6.3 Protein Modification by Proteins and Programmed Protein Degradation 141
6.3.1 Ubiquitin–Proteasome System (UPS) 141
6.3.2 Yeast Proteasomes 147
6.3.3 More Functions for Ubiquitin 150
6.3.4 Ubiquitin-Like Proteins (ULPs) and Cognate Factors 151
6.4 Yeast Protein Kinases and Phosphatases 153
6.4.1 Protein Kinases in Yeast 153
6.4.2 Protein Phosphatases in Yeast 158
6.5 Yeast Helicase Families 159
6.5.1 RNA Helicases in Yeast 166
6.5.2 DNA Helicases in Yeast 168
Further Reading 173
7 Yeast Growth and the Yeast Cell Cycle 175
7.1 Modes of Propagation 175
7.1.1 Vegetative Reproduction 175
7.1.2 Sexual Reproduction 181
7.1.3 Filamentous Growth 181
7.1.4 Yeast Aging and Cell Death 183
7.2 Cell Cycle 186
7.2.1 Dynamics and Regulation of the Cell Cycle 186
7.2.2 Dynamics and Regulation of Mitosis 193
7.3 Meiosis 200
7.3.1 Chromosome Treatment During Meiosis 200
7.3.2 Regulation of Meiosis 201
7.3.3 Checkpoints in Meiosis 202
Further Reading 204
8 Yeast Transport 207
8.1 Intracellular Protein Sorting and Transport 207
8.1.1 “Signal Hypothesis” 207
8.1.2 Central Role of the ER 207
8.1.3 Intracellular Protein Trafficking and Sorting 208
8.2 Nuclear Traffic 221
8.2.1 Nuclear Transport 221
8.2.2 Nuclear mRNA Quality Control 223
8.2.3 Nuclear Export of mRNA 224
8.2.4 Nuclear Dynamics of tRNA 225
8.3 Membrane Transporters in Yeast 226
8.3.1 Transport of Cations 226
8.3.2 Channels and ATPases 226
8.3.3 Ca2þ-Signaling and Transport Pathways in Yeast 227
8.3.4 Transition Metal Transport 228
8.3.5 Anion Transport 232
8.3.6 Nutrient and Ammonium Transport 233
8.3.7 Mitochondrial Transport 235
Further Reading 240
9 Yeast Gene Expression 241
9.1 Transcription and Transcription Factors 241
9.2 RNA Polymerases and Cofactors 241
9.2.1 RNA Polymerase I 242
9.2.2 RNA Polymerase III 243
9.2.3 RNA Polymerase II 245
9.2.4 General Transcription Factors (GTFs) 246
9.2.5 Transcriptional Activators 248
9.3 Transcription and its Regulation 251
9.3.1 Regulatory Complexes 251
9.3.2 Modification of Chromatin During Polymerase II Transcription 254
9.3.3 Nucleosome Positioning 259
9.4 DNA Repair Connected to Transcription 259
9.4.1 Nucleotide Excision Repair (NER) 259
9.4.2 Mismatch Repair 261
9.4.3 Base Excision Repair 261
9.5 Coupling Transcription to Pre-mRNA Processing 261
9.5.1 Polyadenylation 261
9.5.2 Generation of Functional mRNA 263
9.6 Yeast Translation Apparatus 268
9.6.1 Initiation 269
9.6.2 Elongation and Termination 270
9.7 Protein Splicing – Yeast Inteins 271
Further Reading 271
10 Molecular Signaling Cascades and Gene Regulation 273
10.1 Ras–cAMP Signaling Pathway 273
10.2 MAP Kinase Pathways 275
10.2.1 Mating-Type Pathway 275
10.2.2 Filamentation/Invasion Pathway 278
10.2.3 Control of Cell Integrity 279
10.2.4 High Osmolarity Growth Pathway 280
10.2.5 Spore Wall Assembly Pathway 280
10.2.6 Influence of MAP Kinase Pathways in Cell Cycle Regulation 281
10.3 General Control by Gene Repression 281
10.3.1 Ssn6–Tup1 Repression 281
10.3.2 Activation and Repression by Rap1 283
10.4 Gene Regulation by Nutrients 283
10.4.1 TOR System 283
10.4.2 Regulation of Glucose Metabolism 287
10.4.3 Regulation of Galactose Metabolism 289
10.4.4 General Amino Acid Control 290
10.4.5 Regulation of Arginine Metabolism 293
10.5 Stress Responses in Yeast 294
10.5.1 Temperature Stress and Heat-Shock Proteins 294
10.5.2 Oxidative and Chemical Stresses 295
10.5.3 Unfolded Protein Response 298
Further Reading 299
11 Yeast Organellar Biogenesis and Function 301
11.1 Mitochondria 301
11.1.1 Genetic Biochemistry of Yeast Mitochondria 301
11.1.2 Mitochondrial Functions Critical to Cell Viability 303
11.1.3 Biogenesis of Mitochondria: Protein Transport 305
11.1.4 Mitochondrial Quality Control and Remodeling 308
11.2 Peroxisomes 310
11.2.1 What They Are – What They Do 310
11.2.2 Protein Import and Cargo 311
Further Reading 312
12 Yeast Genome and Postgenomic Projects 313
12.1 Yeast Genome Sequencing Project 313
12.1.1 Characteristics of the Yeast Genome 314
12.1.2 Comparison of Genetic and Physical Maps 315
12.1.3 Gene Organization 315
12.1.4 Genetic Redundancy: Gene Duplications 317
12.1.5 Gene Typification and Gene Families 318
12.2 Yeast Functional Genomics 322
12.2.1 Early Functional Analysis of Yeast Genes 322
12.2.2 Yeast Transcriptome 322
12.2.3 Yeast Proteome 324
12.2.4 Yeast Metabolic Networks 327
12.2.5 Genetic Landscape of a Cell 329
12.2.6 Data Analysis Platforms 329
12.3 Yeast Systems Biology 330
12.4 Yeast Synthetic Biology 332
Further Reading 334
13 Disease Genes in Yeast 335
13.1 General Aspects 335
13.1.1 First Approaches 335
13.1.2 Recent Advances 335
13.2 Trinucleotide Repeats and Neurodegenerative Diseases 341
13.2.1 Neurodegenerative Disorders 342
13.2.2 Huntington’s Disease 342
13.2.3 Parkinson’s Disease 343
13.2.4 Alzheimer’s Disease and Tau Biology 343
13.2.5 Other Proteinopathies 344
13.3 Aging and Age-Related Disorders 344
13.4 Mitochondrial Diseases 344
Further Reading 346
14 Yeasts in Biotechnology 347
Paola Branduardi and Danilo Porro
14.1 Introduction 347
14.1.1 Biotechnology Disciplines 347
14.1.2 Microorganisms in Biotechnology 348
14.2 Yeasts: Natural and Engineered Abilities 348
14.2.1 Yeast as a Factory 348
14.2.2 Natural Production 349
14.2.3 Engineered Abilities: Recombinant Production of the First Generation 352
14.2.4 Engineered Abilities: Recombinant Production of the Second Generation 358
14.3 Biopharmaceuticals from Healthcare Industries 359
14.3.1 Human Insulin 359
14.3.2 Other Biopharmaceuticals 361
14.4 Biomedical Research 362
14.4.1 Humanized Yeast Systems for Neurodegenerative Diseases 363
14.4.2 Yeast Models of Human Mitochondrial Diseases 363
14.4.3 Yeast Models for Lipid-Related Diseases 364
14.4.4 Yeasts and Complex Genomes 364
14.5 Environmental Technologies: Cell Surface Display 364
14.6 Physiological Basis for Process Design 366
14.6.1 Process Development 367
14.6.2 Production Process 368
Further Reading 370
15 Hemiascomycetous Yeasts 371
Claude Gaillardin
15.1 Selection of Model Genomes for the Genolevures and Other Sequencing Projects 371
15.2 Ecology, Metabolic Specificities, and Scientific Interest of Selected Species 373
15.2.1 Candida glabrata – A Pathogenic Cousin of S. cerevisiae 373
15.2.2 Lachancea (Saccharomyces) kluyveri – An Opportunistic Anaerobe 375
15.2.3 Kluyveromyces lactis – A Respiro-Fermentative Yeast 376
15.2.4 Eremothecium (Ashbya) gossypii – A Filamentous Plant Pathogen 377
15.2.5 Debaryomyces hansenii – An Osmotolerant Yeast 378
15.2.6 Scheffersomyces (Pichia) stipitis – A Xylose-Utilizing Yeast 379
15.2.7 Komagataella (Pichia) pastoris – A Methanol-Utilizing Yeast 380
15.2.8 Blastobotrys (Arxula) adeninivorans – A Thermotolerant Yeast 381
15.2.9 Yarrowia lipolytica – An Oily Yeast 382
15.3 Differences in Architectural Features and Genetic Outfit 383
15.3.1 Genome Sizes and Global Architecture 383
15.3.2 Chromosome Architecture and Synteny 383
15.3.3 Arrangements of Genetic Elements 385
15.3.4 Gene Families and Diversification of the Protein Repertoires 388
15.3.5 tRNAs and rRNAs 391
15.3.6 Other Noncoding RNAs 392
15.3.7 Introns 393
15.3.8 Transposons 395
15.3.9 Mitochondrial DNA 395
15.3.10 DNA Plasmids 397
15.4 Molecular Evolution of Functions 397
15.4.1 Proteome Diversification and Loss or Gain of Functions 398
15.4.2 Changes in Transcriptional Regulation 400
15.4.3 Changes in Post-Transcriptional Regulations 404
Further Reading 405
16 Yeast Evolutionary Genomics 407
Bernard Dujon
16.1 Specificities of Yeast Populations and Species, and their Evolutionary Consequences 407
16.1.1 Species, Complexes, and Natural Hybrids 407
16.1.2 Reproductive Trade-Offs 408
16.1.3 Preference for Inbreeding 409
16.1.4 Population Structures Examined at the Genomic Level 410
16.1.5 Loss of Heterozygosity and Formation of Chimeras 410
16.1.6 Asymmetrical Growth of Clonal Populations 411
16.2 Gene Duplication Mechanisms and their Evolutionary Consequences 412
16.2.1 Gene Clusters 412
16.2.2 Whole-Genome Duplication 413
16.2.3 Segmental Duplications 414
16.2.4 Retrogenes and Dispersed Paralogs 414
16.3 Other Mechanisms of Gene Formation and Acquisition of Novel Functions 415
16.3.1 Introgression 415
16.3.2 Horizontal Gene Transfer from Bacterial Origin 416
16.3.3 De Novo Gene Formation 417
16.3.4 Integration of Other Sequences in Yeast Chromosomes 418
Further Reading 419
17 Epilog: The Future of Yeast Research 421
Appendix A: References 423
Appendix B: Glossary of Genetic and Taxonomic Nomenclature 425
Appendix C: Online Resources useful in Yeast Research 427
Appendix D: Selected Abbreviations 429
Index 433
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