The cell : a molecular approach / 3rd ed.

Table Of Contents:
Preface xv
Organization and Features of The Cell xvii
Supplements to Accompany The Cell xix
PART I Introduction

1 An Overview of Cells and Cell Research 3(38)

THE ORIGIN AND EVOLUTION OF CELLS 4(11)

The First Cell 4(3)

The Evolution of Metabolism 7(1)

Present-Day Prokaryotes 8(1)

Eukaryotic Cells 9(3)

The Development of Multicellular Organisms 12(3)

CELLS AS EXPERIMENTAL MODELS 15(5)

E. coli 15(1)

Yeasts 16(1)

Dictyostelium discoideum 17(1)

Caenorhabditis elegans 17(1)

Drosophile melanogaster 18(1)

Arabidopsis thaliana 18(1)

Vertebrates 19(1)

TOOLS OF CELL BIOLOGY 20(12)

Light Microscopy 21(4)

Electron Microscopy 25(3)

Subcellular Fractionation 28(1)

Growth of Animal Cells in Culture 29(5)

Culture of Plant Cells 34(1)

Viruses 34

KEY EXPERIMENT Animal Cell Culture 32(3)

MOLECULAR MEDICINE Viruses and Cancer 35(2)

SUMMARY AND KEYTERMS 37(1)

QUESTIONS 38(1)

REFERENCES AND FURTHER READING 39(2)

2 The Chemistry of Cells 41(48)

THE MOLECULAR COMPOSITION OF CELLS 41(15)

Carbohydrates 42(2)

Lipids 44(3)

Nucleic Acids 47(3)

Proteins 50(6)

THE CENTRAL ROLE OF ENZYMES AS BIOLOGICAL CATALYSTS 56(7)

The Catalytic Activity of Enzymes 56(1)

Mechanisms of Enzymatic Catalysis 57(2)

Coenzymes 59(2)

Regulation of Enzyme Activity 61(2)

METABOLIC ENERGY 63(11)

Free Energy and ATP 64(2)

The Generation of ATP from Glucose 66(5)

The Derivation of Energy from Other Organic Molecules 71(1)

Photosynthesis 72(2)

THE BIOSYNTHESIS OF CELL CONSTITUENTS 74(6)

Carbohydrates 74(1)

Lipids 75(1)

Proteins 76(3)

Nucleic Acids 79(1)

CELL MEMBRANES 80

Membrane Lipids 80(1)

Membrane Proteins 81(2)

Transport across Cell Membranes 83

KEY EXPERIMENT The Folding of Polypeptide Chains 52(27)

MOLECULAR MEDICINE Phenylketonuria 79(6)

SUMMARY AND KEYTERMS 85(2)

QUESTIONS 87(1)

REFERENCES AND FURTHER READING 87(2)

3 Fundamentals of Molecular Biology 89(50)

HEREDITY, GENES, AND DNA 89(7)

Genes and Chromosomes 90(1)

Genes and Enzymes 91(2)

Identification of DNA as the Genetic Material 93(1)

The Structure of DNA 94(1)

Replication of DNA 95(1)

EXPRESSION OF GENETIC INFORMATION 96(8)

Colinearity of Genes and Proteins 97(1)

The Role of Messenger RNA 98(1)

The Genetic Code 99(1)

RNA Viruses and Reverse Transcription 100(4)

RECOMBINANT DNA 104(13)

Restriction Endonucleases 104(3)

Generation of Recombinant DNA Molecules 107(1)

Vectors for Recombinant DNA 108(3)

DNA Sequencing 111(2)

Expression of Cloned Genes 113(2)

Amplification of DNA by the Polymerase Chain Reaction 115(2)

DETECTION OF NUCLEIC ACIDS AND PROTEINS 117(6)

Nucleic Acid Hybridization 117(2)

Detection of Small Amounts of DNA or RNA by PCR 119(2)

Antibodies as Probes for Proteins 119 Probes for Screening Recombinant DNA Libraries 121(2)

GENE FUNCTION IN EUKARYOTES 123

Genetic Analysis in Yeasts 123(2)

Gene Transfer in Plants and Animals 125(3)

Mutagenesis of Cloned DNAs 128(1)

Introducing Mutations into Cellular Genes 128

KEY EXPERIMENT The DNA Provirus Hypothesis 102(3)

MOLECULAR MEDICINE HIV and AIDS 105(27)

SUMMARY AND KEY TERMS 132(2)

QUESTIONS 134(1)

REFERENCES AND FURTHER READING 135(4)
PART II The Flow of Genetic Information

4 The Organization and Sequences of Cellular Genomes 139(40)

THE COMPLEXITY OF EUKARYOTIC GENOMES 139(2)

Introns and Exons 141(4)

Repetitive DNA Sequences 145(3)

Gene Duplication and Pseudogenes 148(1)

The Composition of Higher Eukaryotic Genomes 149(1)

CHROMOSOMES AND CHROMATIN 150(8)

Chromatin 150(4)

Centromeres 154(3)

Telomeres 157(1)

THE SEQUENCES OF COMPLETE GENOMES 158

Prokaryotic Genomes 159(2)

The Yeast Genome 161(2)

The Genomes of Caenorhabditis elegans and Drosophile melanogaster 163(2)

Plant Genomes 165(2)

The Human Genome 167

KEY EXPERIMENT The Discovery of introns 142(28)

KEY EXPERIMENT The Human Genome 170(3)

SUMMARY AND KEYTERMS 173(2)

QUESTIONS 175(1)

REFERENCES AND FURTHER READING 175(4)

5 Replication, Maintenance, and Rearrangements of Genomic DNA 179(52)

DNA REPLICATION 179(13)

DNA Polymerases 180(2)

The Replication Fork 182(6)

The Fidelity of Replication 188(1)

Origins and the Initiation of Replication 189(2)

Telomeres and Telomerase: Replicating the Ends of Chromosomes 191(1)

DNA REPAIR 192(12)

Direct Reversal of DNA Damage 194(3)

Excision Repair 197(4)

Error-Prone Repair 201(1)

Recombinational Repair 202(2)

RECOMBINATION BETWEEN HOMOLOGOUS DNA SEQUENCES 204(7)

DNA Molecules Recombine by Breaking and Rejoining 205(2)

Models of Homologous Recombination 207(2)

Enzymes Involved in Homologous Recombination 209(2)

DNA REARRANGEMENTS 211(7)

Site-Specific Recombination 211(5)

Transposition via DNA Intermediates 216(4)

Transposition via RNA Intermediates 220(5)

Gene Amplification 225

KEY EXPERIMENT Rearrangement of Immunoglobulin Genes 218

MOLECULAR MEDICINE Colon Cancer and DNA Repair 203(24)

SUMMARY AND KEYTERMS 227(1)

QUESTIONS 228(1)

REFERENCES AND FURTHER READING 229(2)

6 RNA Synthesis and Processing 231(50)

TRANSCRIPTION IN PROKARYOTES 231(8)

RNA Polymerase and Transcription 232(4)

Repressors and Negative Control of Transcription 236(2)

Positive Control of Transcription 238(1)

EUKARYOTIC RNA POLYMERASES AND GENERAL TRANSCRIPTION FACTORS 239(5)

Eukaryotic RNA Polymerases 239(1)

General Transcription Factors and Initiation of Transcription by RNA Polymerase II 240(3)

Transcription by RNA Polymerases I and III 243(1)

REGULATION OF TRANSCRIPTION IN EUKARYOTES 244(17)

cis-Acting Regulatory Sequences: Promoters and Enhancers 245(4)

Transcriptional Regulatory Proteins 249(3)

Structure and Function of Transcriptional Activators 252(2)

Eukaryotic Repressors 254(2)

Relationship of Chromatin Structure to Transcription 256(3)

Regulation of Transcription by Noncoding RNAs 259(1)

DNA Methylation 260(1)

RNA PROCESSING AND TURNOVER 261

Processing of Ribosomal and Transfer RNAs 262(2)

Processing of mRNA in Eukaryotes 264(2)

Splicing Mechanisms 266(6)

Alternative Splicing 272(1)

RNA Editing 273(1)

RNA Degradation 274

KEY EXPERIMENT Isolation of a Eukaryotic Transcription Factor 251(17)

KEY EXPERIMENT The Discovery of snRNPs 268(8)

SUMMARY AND KEYTERMS 276(2)

QUESTIONS 278(1)

REFERENCES AND FURTHER READING 279(2)

7 Protein Synthesis, Processing, and Regulation 281(42)

TRANSLATION OF mRNA 281(17)

Transfer RNAs 282(1)

The Ribosome 283(6)

The Organization of mRNAs and the Initiation of Translation 289(1)

The Process of Translation 290(6)

Regulation of Translation 296(2)

PROTEIN FOLDING AND PROCESSING 298(11)

Chaperones and Protein Folding 298(5)

Enzymes and Protein Folding 303(1)

Protein Cleavage 303(2)

Glycosylation 305(2)

Attachment of Lipids 307(2)

REGULATION OF PROTEIN FUNCTION 309

Regulation by Small Molecules 310(1)

Protein Phosphorylation 311(2)

Protein-Protein Interactions 313(1)

PROTEIN DEGRADATION 313(1)

The Ubiquitin-Proteasome Pathway 313(2)

Lysosomal Proteolysis 315

KEY EXPERIMENT Catalytic Role of Ribosomal RNA 288(4)

MOLECULAR MEDICINE Antibiotics and Protein Synthesis 292(24)

SUMMARY AND KEYTERMS 316(2)

QUESTIONS 318(1)

REFERENCES AND FURTHER READING 318(5)
PART III Cell Structure and Function

8 The Nucleus 323(32)

THE NUCLEAR ENVELOPE AND TRAFFIC BETWEEN THE NUCLEUS AND CYTOPLASM 323(12)

Structure of the Nuclear Envelope 324(2)

The Nuclear Pore Complex 326(2)

Selective Transport of Proteins to and from the Nucleus 328(4)

Regulation of Nuclear Protein Import 332(2)

Transport of RNAs 334(1)

INTERNAL ORGANIZATION OF THE NUCLEUS 335(4)

Chromosomes and Higher-Order Chromatin Structure 335(2)

Functional Domains within the Nucleus 337(2)

THE NUCLEOLUS 339(6)

Ribosomal RNA Genes and the Organization of the Nucleolus 339(3)

Transcription and Processing of rRNA 342(2)

Ribosome Assembly 344(1)

THE NUCLEUS DURING MITOSIS 345

Dissolution of the Nuclear Envelope 345(3)

Chromosome Condensation 348(1)

Re-formation of the Interphase Nucleus 349

KEY EXPERIMENT Identification of Nuclear Localization Signals 330(10)

MOLECULAR MEDICINE Nuclear Lamina Diseases 340(11)

SUMMARY AND KEYTERMS 351(1)

QUESTIONS 352(1)

REFERENCES AND FURTHER READING 353(2)

9 Protein Sorting and Transport: The Endoplasmic Reticulum, Golgi Apparatus, and Lysosomes 355(44)

THE ENDOPLASMIC RETICULUM 355(19)

The Endoplasmic Reticulum and Protein Secretion 356(1)

Targeting Proteins to the Endoplasmic Reticulum 357(5)

Insertion of Proteins into the ER Membrane 362(4)

Protein Folding and Processing in the ER 366(3)

The Smooth ER and Lipid Synthesis 369(3)

Export of Proteins and Lipids from the ER 372(2)

THE GOLGI APPARATUS 374(8)

Organization of the Golgi 375(2)

Protein Glycosylation within the Golgi 377(2)

Lipid and Polysaccharide Metabolism in the Golgi 379(1)

Protein Sorting and Export from the Golgi Apparatus 380(2)

THE MECHANISM OF VESICULAR TRANSPORT 382

Experimental Approaches to Under standing Vesicular Transport 383(2)

Coat Proteins, Cargo Selection, and Vesicle Budding 385(2)

Vesicle Fusion 387(2)

LYSOSOMES 389(1)

Lysosomal Acid Hydrolases 389(1)

Endocytosis and Lysosome Formation 390(3)

Phagocytosis and Autophagy 393

KEY EXPERIMENT The Signal Hypothesis 360(32)

MOLECULAR MEDICINE Gaucher's Disease 392(2)

SUMMARY AND KEYTERMS 394(2)

QUESTIONS 396(1)

REFERENCES AND FURTHER READING 396(3)

10 Bioenergetics and Metabolism: Mitochondria, Chloroplasts, and Peroxisomes 399(36)

MITOCHONDRIA 399(9)

Organization and Function of Mitochondria 400(1)

The Genetic System of Mitochondria 401(2)

Protein Import and Mitochondrial Assembly 403(5)

THE MECHANISM OF OXIDATIVE PHOSPHORYLATION 408(7)

The Electron Transport Chain 408(2)

Chemiosmotic Coupling 410(4)

Transport of Metabolites across the Inner Membrane 414(1)

CHLOROPLASTS AND OTHER PLASTIDS 415(7)

The Structure and Function of Chloroplasts 415(2)

The Chloroplast Genome 417(1)

Import and Sorting of Chloroplast Proteins 418(2)

Other Plastids 420(2)

PHOTOSYNTHESIS 422

Electron Flow through Photosystems I and II 422(3)

Cyclic Electron Flow 425(1)

ATP Synthesis 426(1)

PEROXISOMES 426(1)

Functions of Peroxisomes 427(2)

Peroxisome Assembly 429

KEY EXPERIMENT The Chemiosmotic Theory 412

MOLECULAR MEDICINE Diseases of Mitochondria: Leber's Hereditary Optic Neuropathy 406(24)

SUMMARY AND KEYTERMS 430(2)

QUESTIONS 432(1)

REFERENCES AND FURTHER READING 433(2)

11 The Cytoskeleton and Cell Movement 435(48)

STRUCTURE AND ORGANIZATION OF ACTIN FILAMENTS 435(12)

Assembly and Disassembly of Actin Filaments 436(4)

Organization of Actin Filaments 440(2)

Association of Actin Filaments with the Plasma Membrane 442(3)

Protrusions of the Cell Surface 445(2)

ACTIN, MYOSIN, AND CELL MOVEMENT 447(8)

Muscle Contraction 447(4)

Contractile Assemblies of Actin and

Myosin in Nonmuscle Cells 451(2)

Unconventional Myosins 453(1)

Cell Migration and Crawling 454(1)

INTERMEDIATE FILAMENTS 455(7)

Intermediate Filament Proteins 455(1)

Assembly of Intermediate Filaments 456(1)

Intracellular Organization of Intermediate Filaments 457(2)

Functions of Keratins and Neurofilaments: Diseases of the Skin and Nervous System 459(3)

MICROTUBULES 462(6)

Structure, Assembly, and Dynamic Instability of Microtubules 462(4)

The Centrosome, Centrioles, and Microtubule Organization 463 Reorganization of Microtubules during Mitosis 466(1)

Stabilization of Microtubules and Cell Polarity 467(1)

MICROTUBULE MOTORS AND MOVEMENTS 468

Identification of Microtubule Motor Proteins 468(4)

Organelle Transport and Intracellular Organization 472(2)

Separation of Mitotic Chromosomes 474(1)

Cilia and Flagella 474

KEY EXPERIMENT Expression of Mutant Keratin Causes Abnormal Skin Development 460(10)

KEY EXPERIMENT The Isolation of Kinesin 470(8)

SUMMARY AND KEYTERMS 478(2)

QUESTIONS 480(1)

REFERENCES AND FURTHER READING 481(2)

12 The Cell Surface 483(58)

STRUCTURE OF THE PLASMA MEMBRANE 483(10)

The Phospholipid Bilayer 483(3)

Membrane Proteins 486(4)

Mobility of Membrane Proteins 490(2)

The Glycocalyx 492(1)

TRANSPORT OF SMALL MOLECULES 493(17)

Passive Diffusion 494(1)

Facilitated Diffusion and Carrier Proteins 494(2)

Ion Channels 496(7)

Active Transport Driven by ATP Hydrolysis 503(4)

Active Transport Driven by Ion Gradients 507(3)

ENDOCYTOSIS 510(8)

Phagocytosis 510(1)

Receptor-Mediated Endocytosis 511(4)

Protein Trafficking in Endocytosis 515(3)

CELL WALLS AND THE EXTRACELLULAR MATRIX 518(10)

Bacterial Cell Walls 518(1)

Plant Cell Walls 519(3)

The Extracellular Matrix 522(6)

CELL-CELL INTERACTIONS 528

Cell Adhesion Proteins 528(3)

Tight Junctions 531(1)

Gap Junctions 532(1)

Plant Cell adhesion and Plasmodesmata 532

KEY EXPERIMENT The LDL Receptor 512

MOLECULAR MEDICINE Cystic Fibrosis 509(24)

SUMMARY AND KEY TERMS 533(2)

QUESTIONS 535(1)

REFERNCES AND FURTHER READING 536(5)
PART IV Cell Regulation

13 Cell Signaling 541(50)

SIGNALING MOLECULES AND THEIR RECEPTORS 541(9)

Modes of Cell-Cell Signaling 542(1)

Steroid Hormones and the Nuclear

Receptor Superfamily 543(2)

Nitric Oxide and Carbon Monoxide 545(1)

Neurotransmitters 546(1)

Peptide Hormones and Growth Factors 546(2)

Eicosanoids 548(1)

Plant Hormones 549(1)

FUNCTIONS OF CELL SURFACE RECEPTORS 550(8)

G Protein-Coupled Receptors 551(2)

Receptor Protein-Tyrosine Kinases 553(4)

Cytokine Receptors and Nonreceptor Protein-Tyrosine Kinases 557(1)

Receptors Linked to Other Enzymatic Activities 557(1)

PATHWAYS OF INTRACELLULAR SIGNAL TRANSDUCTION 558(13)

The cAMP Pathway: Second Messengers and Protein Phosphorylation 559(2)

Cyclic GMP 561(1)

Phospholipids and Cat+ 562(3)

Ras, Raf, and the MAP Kinase Pathway 565(5)

The JAK/STAT Pathway 570(1)

SIGNAL TRANSDUCTION AND THE CYTOSKELETON 571(4)

Integrins and Signal Transduction 571(3)

Regulation of the Actin Cytoskeleton 574(1)

SIGNALING IN DEVELOPMENT AND DIFFERENTIATION 575(4)

The Receptor Tyrosine Kinase/Ras/Raf/ERK Pathway in Drosophile and C. elegans 575(2)

Hedgehog and Wnt 577(1)

Notch Signaling 578(1)

REGULATION OF PROGRAMMED CELL DEATH 579

Caspases and Apoptosis 580(2)

Cell Death Receptors and Caspase Activation 582(1)

Signaling Cell Survival 582

KEY EXPERIMENT The Src Protein-Tyrosine Kinase 554(18)

MOLECULAR MEDICINE Cancer: Signal Transduction, and the ras Oncogenes 572(12)

SUMMARY AND KEYTERMS 584(3)

QUESTIONS 587(1)

REFERENCES AND FURTHER READING 587(4)

14 The Cell Cycle 591(40)

THE EUKARYOTIC CELL CYCLE 591(8)

Phases of the Cell Cycle 592(2)

Regulation of the Cell Cycle by Cell Growth and Extracellular Signals 594(2)

Cell Cycle Checkpoints 596(2)

Restricting DNA Replication to Once per Cell Cycle 598(1)

REGULATORS OF CELL CYCLE PROGRESSION 599(9)

MPF: A Dimer of Cdc2 and Cyclin 599(4)

Families of Cyclins and Cyclin Dependent Kinases 603(2)

Growth Factors and the D-Type Cyclins 605(1)

Inhibitors of Cell Cycle Progression 606(2)

THE EVENTS OF M PHASE 608(7)

Stages of Mitosis 608(3)

MPF and Progression to Metaphase 611(2)

Proteolysis and the Inactivation of MPF: Anaphase and Telophase 613(1)

Cytokinesis 614(1)

MEIOSIS AND FERTILIZATION 615(6)

The Process of Meiosis 615(3)

Regulation of Oocyte Meiosis 618(2)

Fertilization 620(1)

STEM CELLS AND THE MAINTENANCE OF ADULT TISSUES 621

Proliferation of Differentiated Cells 621(1)

Stem Cells 622(2)

Medical Applications of Stem Cells 624

KEY EXPERIMENT The Discovery of MPF 600(22)

KEY EXPERIMENT Culture of Embryonic Stem Cells 622(3)

SUMMARY AND KEYTERMS 625(3)

QUESTIONS 628(1)

REFERENCES AND FURTHER READING 628(3)

15 Cancer 631(44)

THE DEVELOPMENT AND CAUSES OF CANCER 631(9)

Types of Cancer 631(2)

The Development of Cancer 633(1)

Causes of Cancer 634(2)

Properties of Cancer Cells 636(4)

Transformation of Cells in Culture 640(1)

TUMOR VIRUSES 640(4)

Hepatitis B and C Viruses 641(1)

SV40 and Polyomavirus 641(1)

Papillomaviruses 642(1)

Adenoviruses 642(1)

Herpesviruses 643(1)

Retroviruses 644(1)

ONCOGENES 644(13)

Retroviral Oncogenes 645(1)

Proto-Oncogenes 646(3)

Oncogenes in Human Cancer 649(4)

Functions of Oncogene Products 653(4)

TUMOR SUPPRESSOR GENES 657(7)

Identification of Tumor Suppressor Genes 657(3)

Functions of Tumor Suppressor Gene Products 660(3)

Roles of Oncogenes and Tumor Suppressor Genes in Tumor Development 663(1)

APPLICATIONS OF MOLECULAR BIOLOGY TO CANCER PREVENTION AND TREATMENT 664

Prevention and Early Detection 664(1)

Molecular Diagnosis 665(1)

Treatment 666

KEY EXPERIMENT The Discovery of Proto-Oncogenes 648(19)

MOLECULAR MEDICINE STI-571: Cancer Treatment Targeted against the bci/abl Oncogene 667(2)

SUMMARYAND KEYTERMS 669(2)

QUESTIONS 671(1)

REFERENCES AND FURTHER READING 671(4)
Answers to Questions 675(6)
Glossary 681(18)
Index 699