The Cell

by Cooper, Geoffrey M.; Hausman, Robert E.

• ISBN13: 9780878932191
• ISBN10: 0878932194
• Edition: 4th
• Format: Hardcover
• Copyright: 2006-06-30
• Publisher: Sinauer Associates Inc

Summary

Courses in molecular and cellular biology are a cornerstone of undergraduate programs in the life sciences. The material is not only fundamental to all biology, but also represents an exciting and rapidly moving area of science. The Cell: A Molecular Approach provides a solid conceptual framework and an introduction to the experimental nature of contemporary research. The Cell presents current comprehensive science in an accessible and cohesive text that is designed to be mastered in one semester.

Table of Contents

Preface	p. xiv
Organization and Features of The Cell	p. xvi
Media and Supplements to Accompany The Cell	p. xviii
Introduction
An Overview of Cells and Cell Research	p. 3
The Origin and Evolution of Cells	p. 4
The First Cell	p. 4
The Evolution of Metabolism	p. 7
Present-Day Prokaryotes	p. 8
Eukaryotic Cells	p. 9
The Origin of Eukaryotes	p. 10
The Development of Multicellular Organisms	p. 12
Cells as Experimental Models	p. 16
E. coli	p. 16
Yeasts	p. 17
Caenorhabditis elegans	p. 17
Drosophila melanogaster	p. 18
Arabidopsis thaliana	p. 19
Vertebrates	p. 19
Tools of Cell Biology	p. 21
Light Microscopy	p. 21
Electron Microscopy	p. 27
Subcellular Fractionation	p. 30
Growth of Animal Cells in Culture	p. 33
Culture of Plant Cells	p. 36
Viruses	p. 36
Key Experiment: Animal Cell Culture	p. 35
Molecular Medicine: Viruses and Cancer	p. 37
Summary and Key Terms	p. 39
Questions	p. 41
References and Further Reading	p. 41
The Composition of Cells	p. 43
The Molecules of Cells	p. 43
Carbohydrates	p. 44
Lipids	p. 46
Nucleic Acids	p. 50
Proteins	p. 52
Cell Membranes	p. 58
Membrane Lipids	p. 60
Membrane Proteins	p. 61
Transport across Cell Membranes	p. 63
Proteomics: Large-Scale Analysis of Cell Proteins	p. 65
Identification of Cell Proteins	p. 65
Global Analysis of Protein Localization	p. 68
Protein Interactions	p. 69
Key Experiment: The Folding of Polypeptide Chains	p. 54
Key Experiment: The Structure of Cell Membranes	p. 59
Summary and Key Terms	p. 70
Questions	p. 71
References and Further Reading	p. 71
Cell Metabolism	p. 73
The Central Role of Enzymes as Biological Catalysts	p. 73
The Catalytic Activity of Enzymes	p. 73
Mechanisms of Enzymatic Catalysis	p. 74
Coenzymes	p. 78
Regulation of Enzyme Activity	p. 79
Metabolic Energy	p. 81
Free Energy and ATP	p. 81
The Generation of ATP from Glucose	p. 84
The Derivation of Energy from Other Organic Molecules	p. 89
Photosynthesis	p. 90
The Biosynthesis of Cell Constituents	p. 91
Carbohydrates	p. 92
Lipids	p. 93
Proteins	p. 94
Nucleic Acids	p. 97
Key Experiment: Antimetabolites and Chemotherapy	p. 98
Molecular Medicine: Phenylketonuria	p. 96
Summary and Key Terms	p. 100
Questions	p. 101
References and Further Reading	p. 101
Fundamentals of Molecular Biology	p. 103
Heredity, Genes, and DNA	p. 103
Genes and Chromosomes	p. 104
Genes and Enzymes	p. 107
Identification of DNA as the Genetic Material	p. 107
The Structure of DNA	p. 108
Replication of DNA	p. 110
Expression of Genetic Information	p. 111
Colinearity of Genes and Proteins	p. 111
The Role of Messenger RNA	p. 112
The Genetic Code	p. 113
RNA Viruses and Reverse Transcription	p. 115
Recombinant DNA	p. 118
Restriction Endonucleases	p. 118
Generation of Recombinant DNA Molecules	p. 121
Vectors for Recombinant DNA	p. 122
DNA Sequencing	p. 125
Expression of Cloned Genes	p. 126
Detection of Nucleic Acids and Proteins	p. 129
Amplification of DNA by the Polymerase Chain Reaction	p. 129
Nucleic Acid Hybridization	p. 131
Antibodies as Probes for Proteins	p. 134
Gene Function in Eukaryotes	p. 137
Genetic Analysis in Yeasts	p. 137
Gene Transfer in Plants and Animals	p. 139
Mutagenesis of Cloned DNAs	p. 142
Introducing Mutations into Cellular Genes	p. 142
Interfering with Cellular Gene Expression	p. 145
Key Experiment: The DNA Provirus Hypothesis	p. 116
Molecular Medicine: HIV and AIDS	p. 120
Summary and Key Terms	p. 147
Questions	p. 149
References and Further Reading	p. 150
The Flow of Genetic Information
The Organization and Sequences of Cellular Genomes	p. 155
The Complexity of Eukaryotic Genomes	p. 155
Introns and Exons	p. 157
Repetitive DNA Sequences	p. 161
Gene Duplication and Pseudogenes	p. 164
The Composition of Higher Eukaryotic Genomes	p. 165
Chromosomes and Chromatin	p. 166
Chromatin	p. 166
Centromeres	p. 171
Telomeres	p. 175
The Sequences of Complete Genomes	p. 176
Prokaryotic Genomes	p. 177
The Yeast Genome	p. 178
The Genomes of Caenorhabditis elegans and Drosophila melanogaster	p. 180
Plant Genomes	p. 183
The Human Genome	p. 185
The Genomes of Other Vertebrates	p. 190
Bioinformatics and Systems Biology	p. 192
Systematic Screens of Gene Function	p. 193
Regulation of Gene Expression	p. 194
Variation among Individuals and Genomic Medicine	p. 195
Key Experiment: The Discovery of Introns	p. 158
Key Experiment: The Human Genome	p. 188
Summary and Key Terms	p. 196
Questions	p. 198
References and Further Reading	p. 199
Replication, Maintenance, and Rearrangements of Genomic DNA	p. 201
DNA Replication	p. 202
DNA Polymerases	p. 202
The Replication Fork	p. 202
The Fidelity of Replication	p. 209
Origins and the Initiation of Replication	p. 211
Telomeres and Telomerase: Maintaining the Ends of Chromosomes	p. 214
DNA Repair	p. 216
Direct Reversal of DNA Damage	p. 216
Excision Repair	p. 219
Translesion DNA Synthesis	p. 223
Recombinational Repair	p. 225
Recombination between Homologous DNA Sequences	p. 227
Models of Homologous Recombination	p. 228
Enzymes Involved in Homologous Recombination	p. 229
DNA Rearrangements	p. 233
Site-Specific Recombination	p. 233
Transposition via DNA Intermediates	p. 239
Transposition via RNA Intermediates	p. 242
Gene Amplification	p. 247
Key Experiment: Rearrangement of Immunoglobulin Genes	p. 240
Molecular Medicine: Colon Cancer and DNA Repair	p. 224
Summary and Key Terms	p. 249
Questions	p. 250
References and Further Reading	p. 251
RNA Synthesis and Processing	p. 253
Transcription in Prokaryotes	p. 254
RNA Polymerase and Transcription	p. 254
Repressors and Negative Control of Transcription	p. 258
Positive Control of Transcription	p. 261
Eukaryotic RNA Polymerases and General Transcription Factors	p. 262
Eukaryotic RNA Polymerases	p. 262
General Transcription Factors and Initiation of Transcription by RNA Polymerase II	p. 262
Transcription by RNA Polymerases I and III	p. 266
Regulation of Transcription in Eukaryotes	p. 268
cis-Acting Regulatory Sequences: Promoters and Enhancers	p. 269
Transcription Factor Binding Sites	p. 272
Transcriptional Regulatory Proteins	p. 273
Structure and Function of Transcriptional Activators	p. 277
Eukaryotic Repressors	p. 280
Relationship of Chromatin Structure to Transcription	p. 281
Regulation of Transcription by Noncoding RNAs	p. 285
DNA Methylation	p. 286
RNA Processing and Turnover	p. 287
Processing of Ribosomal and Transfer RNAs	p. 287
Processing of mRNA in Eukaryotes	p. 290
Splicing Mechanisms	p. 292
Alternative Splicing	p. 299
RNA Editing	p. 300
RNA Degradation	p. 301
Key Experiment: Isolation of a Eukaryotic Transcription Factor	p. 276
Key Experiment: The Discovery of snRNPs	p. 294
Summary and Key Terms	p. 303
Questions	p. 306
References and Further Reading	p. 306
Protein Synthesis, Processing, and Regulation	p. 309
Translation of mRNA	p. 309
Transfer RNAs	p. 310
The Ribosome	p. 311
The Organization of mRNAs and the Initiation of Translation	p. 317
The Process of Translation	p. 319
Regulation of Translation	p. 325
Protein Folding and Processing	p. 329
Chaperones and Protein Folding	p. 330
Enzymes that Catalyze Protein Folding	p. 332
Protein Cleavage	p. 333
Glycosylation	p. 335
Attachment of Lipids	p. 337
Regulation of Protein Function	p. 339
Regulation by Small Molecules	p. 340
Protein Phosphorylation	p. 341
Protein-Protein Interactions	p. 344
Protein Degradation	p. 344
The Ubiquitin-Proteasome Pathway	p. 344
Lysosomal Proteolysis	p. 347
Key Experiment: Catalytic Role of Ribosomal RNA	p. 316
Molecular Medicine: Antibiotic Resistance and the Ribosome	p. 320
Summary and Key Terms	p. 348
Questions	p. 350
References and Further Reading	p. 350
Cell Structure and Function
The Nucleus	p. 355
The Nuclear Envelope and Traffic between the Nucleus and the Cytoplasm	p. 355
Structure of the Nuclear Envelope	p. 356
The Nuclear Pore Complex	p. 361
Selective Transport of Proteins to and from the Nucleus	p. 362
Regulation of Nuclear Protein Import	p. 368
Transport of RNAs	p. 369
Internal Organization of the Nucleus	p. 371
Chromosomes and Higher-Order Chromatin Structure	p. 371
Sub-Compartments within the Nucleus	p. 374
The Nucleolus and rRNA Processing	p. 375
Ribosomal RNA Genes and the Organization of the Nucleolus	p. 376
Transcription and Processing of rRNA	p. 377
Ribosome Assembly	p. 379
Key Experiment: Nuclear Lamina Diseases	p. 359
Molecular Medicine: Identification of Nuclear Localization Signals	p. 364
Summary and Key Terms	p. 380
Questions	p. 382
References and Further Reading	p. 382
Protein Sorting and Transport: The Endoplasmic Reticulum, Golgi Apparatus, and Lysosomes	p. 385
The Endoplasmic Reticulum	p. 386
The Endoplasmic Reticulum and Protein Secretion	p. 386
Targeting Proteins to the Endoplasmic Reticulum	p. 387
Insertion of Proteins into the ER Membrane	p. 393
Protein Folding and Processing in the ER	p. 398
Quality Control in the ER	p. 400
The Smooth ER and Lipid Synthesis	p. 403
Export of Proteins and Lipids from the ER	p. 406
The Golgi Apparatus	p. 408
Organization of the Golgi	p. 409
Protein Glycosylation within the Golgi	p. 410
Lipid and Polysaccharide Metabolism in the Golgi	p. 413
Protein Sorting and Export from the Golgi Apparatus	p. 414
The Mechanism of Vesicular Transport	p. 417
Experimental Approaches to Understanding Vesicular Transport	p. 417
Cargo Selection, Coat Proteins, and Vesicle Budding	p. 419
Vesicle Fusion	p. 420
Lysosomes	p. 424
Lysosomal Acid Hydrolases	p. 424
Endocytosis and Lysosome Formation	p. 424
Phagocytosis and Autophagy	p. 428
Key Experiment: The Signal Hypothesis	p. 390
Molecular Medicine: Gaucher Disease	p. 426
Summary and Key Terms	p. 431
Questions	p. 431
References and Further Reading	p. 431
Bioenergetics and Metabolism: Mitochondria, Chloroplasts, and Peroxisomes	p. 433
Mitochondria	p. 434
Organization and Function of Mitochondria	p. 434
The Genetic System of Mitochondria	p. 435
Protein Import and Mitochondrial Assembly	p. 437
The Mechanism of Oxidative Phosphorylation	p. 443
The Electron Transport Chain	p. 444
Chemiosmotic Coupling	p. 445
Transport of Metabolites across the Inner Membrane	p. 450
Chloroplasts and Other Plastids	p. 451
The Structure and Function of Chloroplasts	p. 451
The Chloroplast Genome	p. 452
Import and Sorting of Chloroplast Proteins	p. 454
Other Plastids	p. 456
Photosynthesis	p. 458
Electron Flow through Photosystems I and II	p. 459
Cyclic Electron Flow	p. 461
ATP Synthesis	p. 462
Peroxisomes	p. 462
Functions of Peroxisomes	p. 463
Peroxisome Assembly	p. 465
Key Experiment: The Chemiosmotic Theory	p. 448
Molecular Medicine: Diseases of Mitochondria: Leber's Hereditary Optic Neuropathy	p. 438
Summary and Key Terms	p. 467
Questions	p. 469
References and Further Reading	p. 470
The Cytoskeleton and Cell Movement	p. 473
Structure and Organization of Actin Filaments	p. 473
Assembly and Disassembly of Actin Filaments	p. 474
Organization of Actin Filaments	p. 480
Association of Actin Filaments with the Plasma Membrane	p. 482
Protrusions of the Cell Surface	p. 485
Actin, Myosin, and Cell Movement	p. 486
Muscle Contraction	p. 487
Contractile Assemblies of Actin and Myosin in Nonmuscle Cells	p. 491
Nonmuscle Myosins	p. 493
Formation of Protrusions and Cell Movement	p. 495
Intermediate Filaments	p. 497
Intermediate Filament Proteins	p. 497
Assembly of Intermediate Filaments	p. 498
Intracellular Organization of Intermediate Filaments	p. 499
Functions of Keratins and Neurofilaments: Diseases of the Skin and Nervous System	p. 502
Microtubules	p. 505
Structure and Dynamic Organization of Microtubules	p. 505
Assembly of Microtubules	p. 507
Organization of Microtubules within Cells	p. 510
Microtubule Motors and Movement	p. 511
Identification of Microtubule Motor Proteins	p. 511
Cargo Transport and Intracellular Organization	p. 514
Cilia and Flagella	p. 517
Reorganization of Microtubules during Mitosis	p. 520
Chromosome Movement	p. 521
Key Experiment: Expression of Mutant Keratin Causes Abnormal Skin Development	p. 502
Key Experiment The Isolation of Kinesin	p. 514
Summary and Key Terms	p. 523
Questions	p. 526
References and Further Reading	p. 526
The Plasma Membrane	p. 529
Structure of the Plasma Membrane	p. 529
The Phospholipid Bilayer	p. 530
Membrane Proteins	p. 532
Mobility of Membrane Proteins	p. 537
The Glycocalyx	p. 540
Transport of Small Molecules	p. 540
Passive Diffusion	p. 541
Facilitated Diffusion and Carrier Proteins	p. 542
Ion Channels	p. 543
Active Transport Driven by ATP Hydrolysis	p. 550
Active Transport Driven by Ion Gradients	p. 555
Endocytosis	p. 556
Phagocytosis	p. 557
Receptor-Mediated Endocytosis	p. 558
Protein Trafficking in Endocytosis	p. 563
Key Experiment: The LDL Receptor	p. 559
Molecular Medicine: Cystic Fibrosis	p. 554
Summary and Key Terms	p. 566
Questions	p. 567
References and Further Reading	p. 567
Cell Walls, the Extracellular Matrix, and Cell Interactions	p. 569
Cell Wall	p. 569
Bacterial Cell Walls	p. 570
Eukaryotic Cell Walls	p. 570
The Extracellular Matrix and Cell-Matrix Interactions	p. 575
Matrix Structural Proteins	p. 575
Matrix Polysaccharides	p. 578
Matrix Adhesion Proteins	p. 579
Cell-Matrix Interactions	p. 580
Cell-Cell Interactions	p. 584
Adhesion Junctions	p. 584
Tight Junctions	p. 588
Gap Junctions	p. 589
Plasmodesmata	p. 592
Key Experiment: The Characterization of Integrin	p. 582
Molecular Medicine: Gap Junction Diseases	p. 591
Summary and Key Terms	p. 593
Questions	p. 594
References and Further Reading	p. 595
Cell Regulation
Cell Signaling	p. 599
Signaling Molecules and Their Receptors	p. 600
Modes of Cell-Cell Signaling	p. 600
Steroid Hormones and the Nuclear Receptor Superfamily	p. 601
Nitric Oxide and Carbon Monoxide	p. 603
Neurotransmitters	p. 604
Peptide Hormones and Growth Factors	p. 605
Eicosanoids	p. 607
Plant Hormones	p. 608
Functions of Cell Surface Receptors	p. 609
G Protein-Coupled Receptors	p. 610
Receptor Protein-Tyrosine Kinases	p. 612
Cytokine Receptors and Nonreceptor Protein-Tyrosine Kinases	p. 616
Receptors Linked to Other Enzymatic Activities	p. 616
Pathways of Intracellular Signal Transduction	p. 617
The cAMP Pathway: Second Messengers and Protein Phosphorylation	p. 618
Cyclic GMP	p. 620
Phospholipids and Ca[superscript 2+]	p. 621
The PI 3-Kinase/Akt and mTOR Pathways	p. 624
MAP Kinase Pathways	p. 627
The JAK/STAT and TGF-[beta]/Smad Pathways	p. 633
NF-[kappa]B Signaling	p. 634
The Hedgehog, Wnt, and Notch Pathways	p. 634
Signal Transduction and the Cytoskeleton	p. 637
Integrins and Signal Transduction	p. 637
Regulation of the Actin Cytoskeleton	p. 638
Signaling Networks	p. 640
Feedback and Crosstalk	p. 640
Networks of Cellular Signal Transduction	p. 641
Key Experiment: The Src Protein-Tyrosine Kinase	p. 612
Molecular Medicine: Cancer: Signal Transduction and the ras Oncogenes	p. 629
Summary and Key Terms	p. 643
Questions	p. 646
References and Further Reading	p. 646
The Cell Cycle	p. 649
The Eukaryotic Cell Cycle	p. 650
Phases of the Cell Cycle	p. 650
Regulation of the Cell Cycle by Cell Growth and Extracellular Signals	p. 652
Cell Cycle Checkpoints	p. 654
Restricting DNA Replication to Once per Cell Cycle	p. 656
Regulators of Cell Cycle Progression	p. 657
Protein Kinases and Cell Cycle Regulation	p. 657
Families of Cyclins and Cyclin-Dependent Kinases	p. 661
Growth Factors and the Regulation of G[subscript 1] Cdk's	p. 665
DNA Damage Checkpoints	p. 667
The Events of M Phase	p. 669
Stages of Mitosis	p. 669
Cdk1/Cyclin B and Progression to Metaphase	p. 672
The Spindle Assembly Checkpoint and Progression to Anaphase	p. 675
Cytokinesis	p. 677
Meiosis and Fertilization	p. 678
The Process of Meiosis	p. 678
Regulation of Oocyte Meiosis	p. 681
Fertilization	p. 684
Key Experiment: The Discovery of MPF	p. 658
Key Experiment: The Identification of Cyclin	p. 662
Summary and Key Terms	p. 685
Questions	p. 687
References and Further Reading	p. 687
Cell Death and Cell Renewal	p. 689
Programmed Cell Death	p. 690
The Events of Apoptosis	p. 690
Caspases: The Executioners of Apoptosis	p. 692
Central Regulators of Apoptosis: The Bcl-2 Family	p. 695
Signaling Pathways that Regulate Apoptosis	p. 698
Stem Cells and the Maintenance of Adult Tissues	p. 700
Proliferation of Differentiated Cells	p. 700
Stem Cells	p. 703
Medical Applications of Adult Stem Cells	p. 708
Embryonic Stem Cells and Therapeutic Cloning	p. 709
Embryonic Stem Cells	p. 710
Somatic Cell Nuclear Transfer	p. 713
Key Experiment: Identification of Genes Required for Programmed Cell Death	p. 694
Key Experiment: Culture of Embryonic Stem Cells	p. 710
Summary and Key Terms	p. 716
Questions	p. 717
References and Further Reading	p. 717
Cancer	p. 719
The Development and Causes of Cancer	p. 719
Types of Cancer	p. 720
The Development of Cancer	p. 721
Causes of Cancer	p. 723
Properties of Cancer Cells	p. 724
Transformation of Cells in Culture	p. 728
Tumor Viruses	p. 729
Hepatitis B and C Viruses	p. 729
SV40 and Polyomavirus	p. 730
Papillomaviruses	p. 731
Adenoviruses	p. 731
Herpesviruses	p. 732
Retroviruses	p. 732
Oncogenes	p. 733
Retroviral Oncogenes	p. 734
Proto-Oncogenes	p. 735
Oncogenes in Human Cancer	p. 738
Functions of Oncogene Products	p. 741
Tumor Suppressor Genes	p. 746
Identification of Tumor Suppressor Genes	p. 746
Functions of Tumor Suppressor Gene Products	p. 750
Roles of Oncogenes and Tumor Suppressor Genes in Tumor Development	p. 753
Molecular Approaches to Cancer Treatment	p. 755
Prevention and Early Detection	p. 755
Molecular Diagnosis	p. 756
Treatment	p. 756
Key Experiment: The Discovery of Proto-Oncogenes	p. 737
Molecular Medicine STI-571: Cancer Treatment Targeted against the bcr/abl Oncogene	p. 759
Summary and Key Terms	p. 761
Questions	p. 763
References and Further Reading	p. 763
Answers to Questions	p. 767
Glossary	p. 779
Index	p. 799
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