THE CELL A Molecular Approach Sixth Edition Geoffrey M. Cooper • Robert E. Hausman Boston University Sinauer Associates, Inc. • Publishers Sunderland, Massachusetts U.S.A. ©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher.
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The Cell - A Molecular Approach, Fifth edition,
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THE CELLA Molecular Approach
Sixth Edition
Geoffrey M. Cooper • Robert E. HausmanBoston University
Sinauer Associates, Inc. • PublishersSunderland, Massachusetts U.S.A.
©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufacturedor disseminated in any form without express written permission from the publisher.
Brief Contents
PART IIntroduction 1
Chapter 1 An Overview of Cells and Cell Research 3
Chapter 2 The Composition of Cells 43
Chapter 3 Cell Metabolism 73
Chapter 4 Fundamentals of Molecular Biology 103
PART IIThe Flow of Genetic Information 151
Chapter 5 The Organization and Sequences of Cellular Genomes 153
Chapter 6 Replication, Maintenance, and Rearrangements of Genomic DNA 191
Chapter 7 RNA Synthesis and Processing 239
Chapter 8 Protein Synthesis, Processing, and Regulation 297
PART IIICell Structure and Function 343
Chapter 9 The Nucleus 345
Chapter 10 Protein Sorting and Transport 373
Chapter 11 Bioenergetics and Metabolism 421
Chapter 12 The Cytoskeleton and Cell Movement 459
Chapter 13 The Plasma Membrane 515
Chapter 14 Cell Walls, the Extracellular Matrix, and Cell Interactions 557
PART IVCell Regulation 587
Chapter 15 Cell Signaling 589
Chapter 16 The Cell Cycle 641
Chapter 17 Cell Death and Cell Renewal 681
Chapter 18 Cancer 713
©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufacturedor disseminated in any form without express written permission from the publisher.
ContentsPreface xix
Organization and Features of The Cell xxi
Media and Supplements to Accompany The Cell xxiii
Part I Introduction 1
CHAPTER 1
An Overview of Cells and Cell Research 3The Origin and Evolution of Cells 4
The first cell 4The evolution of metabolism 6Present-day prokaryotes 8Eukaryotic cells 9The origin of eukaryotes 10The development of multicellular organisms 13
Cells as Experimental Models 17E. coli 17Yeasts 18Caenorhabditis elegans 18Drosophila melanogaster 19Arabidopsis thaliana 19Vertebrates 20
Tools of Cell Biology 22Light microscopy 22Electron microscopy 28Subcellular fractionation 31Growth of animal cells in culture 32Culture of plant cells 36Viruses 36
KEY EXPERIMENT
Animal Cell Culture 34MOLECULAR MEDICINE
Viruses and Cancer 37
Summary and Key Terms 39Questions 40References and Further Reading 41
CHAPTER 2
The Composition of Cells 43The Molecules of Cells 43
Carbohydrates 44Lipids 46Nucleic acids 49Proteins 52
Cell Membranes 58Membrane lipids 58Membrane proteins 59Transport across cell membranes 62
Proteomics: Large-Scale Analysis of Cell Proteins 65
Identification of cell proteins 65Global analysis of protein localization 67Protein interactions 68
©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufacturedor disseminated in any form without express written permission from the publisher.
Contents ix
KEY EXPERIMENT
The Folding of Polypeptide Chains 54KEY EXPERIMENT
The Structure of Cell Membranes 62
Summary and Key Terms 70Questions 71References and Further Reading 71
CHAPTER 3
Cell Metabolism 73The Central Role of Enzymes as Biological
Catalysts 73The catalytic activity of enzymes 73Mechanisms of enzymatic catalysis 74Coenzymes 76Regulation of enzyme activity 79
Metabolic Energy 81Free energy and ATP 81The generation of ATP from glucose 84The derivation of energy from other organic
molecules 89Photosynthesis 90
The Biosynthesis of Cell Constituents 91Carbohydrates 92Lipids 93Proteins 94Nucleic acids 98
KEY EXPERIMENT
Antimetabolites and Chemotherapy 97MOLECULAR MEDICINE
Phenylketonuria 98
Summary and Key Terms 99Questions 100References and Further Reading 101
CHAPTER 4
Fundamentals of Molecular Biology 103Heredity, Genes, and DNA 103
Genes and chromosomes 103Genes and enzymes 105Identification of DNA as the genetic material 107The structure of DNA 108Replication of DNA 109
Expression of Genetic Information 110Colinearity of genes and proteins 111The role of messenger RNA 112The genetic code 113RNA viruses and reverse transcription 115
Recombinant DNA 118Restriction endonucleases 118Generation of recombinant DNA molecules 120Vectors for recombinant DNA 122DNA sequencing 124Expression of cloned genes 126
Detection of Nucleic Acids and Proteins 127Amplification of DNA by the polymerase chain
reaction 127Nucleic acid hybridization 129Antibodies as probes for proteins 132
Gene Function in Eukaryotes 135Genetic analysis in yeasts 135Gene transfer in plants and animals 136Mutagenesis of cloned DNAs 139Introducing mutations into cellular genes 140Interfering with cellular gene expression 142
KEY EXPERIMENT
The DNA Provirus Hypothesis 117KEY EXPERIMENT
RNA Interference 144
Summary and Key Terms 146Questions 148References and Further Reading 148
©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufacturedor disseminated in any form without express written permission from the publisher.
x Contents
Part II The Flow of Genetic Information 151
CHAPTER 5
The Organization and Sequences of Cellular Genomes 153The Complexity of Eukaryotic Genomes 153
Introns and exons 155Repetitive DNA sequences 159Gene duplication and pseudogenes 161
The Sequences of Complete Genomes 162The genomes of bacteria and yeast 163The genomes of Caenorhabditis elegans, Drosophila
melanogaster, and other invertebrates 165Plant genomes 166The human genome 166The genomes of other vertebrates 169
Chromosomes and Chromatin 171Chromatin 172Centromeres 176Telomeres 180
Bioinformatics and Systems Biology 181Systematic screens of gene function 181Regulation of gene expression 182Variation among individuals and genomic
medicine 184KEY EXPERIMENT
The Discovery of Introns 156KEY EXPERIMENT
The Human Genome 167
Summary and Key Terms 186Questions 187References and Further Reading 188
CHAPTER 6
Replication, Maintenance, and Rearrangements of Genomic DNA 191DNA Replication 191
DNA polymerases 192The replication fork 193The fidelity of replication 200Origins and the initiation of replication 201Telomeres and telomerase: maintaining the
ends of chromosomes 205
DNA Repair 207Direct reversal of DNA damage 208Excision repair 210Base-excision repair 210Nucleotide-excision repair 210Transcription-coupled repair 213Mismatch repair 213Translesion DNA synthesis 216Repair of double-strand breaks 216
DNA Rearrangements 219Site-specific recombination 219Transposition via DNA intermediates 227Transposition via RNA intermediates 228Gene amplification 232
MOLECULAR MEDICINE
Colon Cancer and DNA Repair 215KEY EXPERIMENT
Rearrangement of Immunoglobulin Genes 220
©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufacturedor disseminated in any form without express written permission from the publisher.
Contents xi
Summary and Key Terms 233Questions 235References and Further Reading 236
CHAPTER 7
RNA Synthesis and Processing 239Transcription in Prokaryotes 239
RNA polymerase and transcription 240Repressors and negative control of
transcription 243Positive control of transcription 245
Eukaryotic RNA Polymerases and General Transcription Factors 245
Eukaryotic RNA polymerases 246General transcription factors and initiation
of transcription by RNA polymerase II 246Transcription by RNA polymerases I and III 250
Regulation of Transcription in Eukaryotes 251
cis-acting regulatory sequences: promoters and enhancers 251
Transcription factor binding sites 255Transcriptional regulatory proteins 258Structure and function of transcriptional
activators 260Eukaryotic repressors 263Regulation of elongation 264Relationship of chromatin structure to
transcription 266Regulation of transcription by noncoding RNAs 271DNA methylation 273
RNA Processing and Turnover 275Processing of ribosomal and transfer RNAs 275Processing of mRNA in eukaryotes 277Splicing mechanisms 279Alternative splicing 286RNA editing 288RNA degradation 289
KEY EXPERIMENT
Isolation of a Eukaryotic Transcription Factor 259KEY EXPERIMENT
The Discovery of snRNPs 284
Summary and Key Terms 291Questions 293References and Further Reading 294
CHAPTER 8
Protein Synthesis, Processing, and Regulation 297Translation of mRNA 297
Transfer RNAs 298The ribosome 299The organization of mRNAs and the initiation of
translation 305The process of translation 307Regulation of translation 313
Protein Folding and Processing 319Chaperones and protein folding 319Enzymes that catalyze protein folding 322Protein cleavage 323Glycosylation 325Attachment of lipids 327
Regulation of Protein Function 329Regulation by small molecules 329Protein phosphorylation and other
modifications 330Protein-protein interactions 335
Protein Degradation 335The ubiquitin-proteasome pathway 335Lysosomal proteolysis 338
KEY EXPERIMENT
Catalytic Role of Ribosomal RNA 304KEY EXPERIMENT
The Discovery of Protein-Tyrosine Kinases 333
Summary and Key Terms 339Questions 340References and Further Reading 341
©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufacturedor disseminated in any form without express written permission from the publisher.
xii Contents
Part III Cell Structure and Function 343
CHAPTER 9
The Nucleus 345The Nuclear Envelope and Traffic between
the Nucleus and the Cytoplasm 345Structure of the nuclear envelope 346The nuclear pore complex 350Selective transport of proteins to and from the
nucleus 353Regulation of nuclear protein import 356Transport of RNAs 357
Internal Organization of the Nucleus 359Chromosome organization and gene expression 359Sub-compartments within the nucleus 362
The Nucleolus and rRNA Processing 365Ribosomal RNA genes and the organization of the
nucleolus 365Transcription and processing of rRNA 367Ribosome assembly 368Additional functions of the nucleolus 369
MOLECULAR MEDICINE
Nuclear Lamina Diseases 348KEY EXPERIMENT
Identification of Nuclear Localization Signals 352Summary and Key Terms 370Questions 371References and Further Reading 372
CHAPTER 10
Protein Sorting and Transport 373The Endoplasmic Reticulum 373
The endoplasmic reticulum and protein secretion 374
Targeting proteins to the endoplasmic reticulum 376Insertion of proteins into the ER membrane 381Protein folding and processing in the ER 386Quality control in the ER 389The smooth ER and lipid synthesis 392Export of proteins and lipids from the ER 395
The Golgi Apparatus 398Organization of the Golgi 398Protein glycosylation within the Golgi 400Lipid and polysaccharide metabolism in the
Golgi 402Protein sorting and export from the Golgi
apparatus 403
The Mechanism of Vesicular Transport 406Experimental approaches to understanding vesicular
transport 406Cargo selection, coat proteins, and
vesicle budding 407Vesicle fusion 410
Lysosomes 412Lysosomal acid hydrolases 412Endocytosis and lysosome formation 414Phagocytosis and autophagy 416
©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufacturedor disseminated in any form without express written permission from the publisher.
Contents xiii
KEY EXPERIMENT
The Signal Hypothesis 378MOLECULAR MEDICINE
Gaucher Disease 413
Summary and Key Terms 417Questions 419References and Further Reading 419
CHAPTER 11
Bioenergetics and Metabolism 421Mitochondria 421
Organization and function of mitochondria 422The genetic system of mitochondria 424Protein import and mitochondrial assembly 425
The Mechanism of Oxidative Phosphorylation 431
The electron transport chain 431Chemiosmotic coupling 432Transport of metabolites across the inner
membrane 436
Chloroplasts and Other Plastids 438The structure and function of chloroplasts 438The chloroplast genome 440Import and sorting of chloroplast proteins 441Other plastids 444
Photosynthesis 446Electron transport 446ATP synthesis 449
Peroxisomes 450Functions of peroxisomes 451Peroxisome assembly 453
MOLECULAR MEDICINE
Diseases of Mitochondria: Leber’s Hereditary Optic Neuropathy 426
KEY EXPERIMENT
The Chemiosmotic Theory 434
Summary and Key Terms 455
Questions 457References and Further Reading 458
CHAPTER 12
The Cytoskeleton and Cell Movement 459Structure and Organization of Actin
Filaments 459Assembly and disassembly of actin filaments 460Organization of actin filaments 465Association of actin filaments with the plasma
membrane 467Protrusions of the cell surface 471
Actin, Myosin, and Cell Movement 472Muscle contraction 473Contractile assemblies of actin and myosin in
nonmuscle cells 477Unconventional myosins 479Formation of protrusions and cell movement 480
Microtubules 482Structure and dynamic organization of
microtubules 482Assembly of microtubules 485Organization of microtubules within cells 488
Microtubule Motors and Movement 490Identification of microtubule motor proteins 490Cargo transport and intracellular organization 493Cilia and flagella 496Reorganization of microtubules during mitosis 499Chromosome movement 500
Intermediate Filaments 502Intermediate filament proteins 502Assembly of intermediate filaments 504Intracellular organization of intermediate
filaments 505Functions of intermediate filaments: keratins and
diseases of the skin 507KEY EXPERIMENT
The Isolation of Kinesin 491
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xiv Contents
KEY EXPERIMENT
Expression of Mutant Keratin Causes Abnormal Skin Development 508
Summary and Key Terms 510Questions 512References and Further Reading 512
CHAPTER 13
The Plasma Membrane 515Structure of the Plasma Membrane 515
The phospholipid bilayer 515Membrane proteins 519Mobility of membrane proteins 524The glycocalyx 525
Transport of Small Molecules 526Passive diffusion 526Facilitated diffusion and carrier proteins 527Ion channels 529Active transport driven by ATP hydrolysis 537Active transport driven by ion gradients 540
Endocytosis 544Phagocytosis 544Receptor-mediated endocytosis 545Protein trafficking in endocytosis 550
MOLECULAR MEDICINE
Cystic Fibrosis 541KEY EXPERIMENT
The LDL Receptor 548
Summary and Key Terms 553Questions 554References and Further Reading 555
CHAPTER 14
Cell Walls, the Extracellular Matrix, and Cell Interactions 557Cell Walls 557
Bacterial cell walls 557Eukaryotic cell walls 557
The Extracellular Matrix and Cell-Matrix Interactions 564
Matrix structural proteins 564Matrix polysaccharides 568Matrix adhesion proteins 569Cell-matrix interactions 571
Cell-Cell Interactions 574Adhesion junctions 574Tight junctions 577Gap junctions 578Plasmodesmata 581
KEY EXPERIMENT
The Characterization of Integrin 572MOLECULAR MEDICINE
Gap Junction Diseases 580
Summary and Key Terms 582Questions 583References and Further Reading 584
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Contents xv
Part IV Cell Regulation 587
CHAPTER 15
Cell Signaling 589Signaling Molecules and Their
Receptors 589Modes of cell-cell signaling 590Steroid hormones and the nuclear receptor
superfamily 591Nitric oxide and carbon monoxide 593Neurotransmitters 594Peptide hormones and growth factors 594Eicosanoids 596Plant hormones 598
Functions of Cell Surface Receptors 599G protein-coupled receptors 600Receptor protein-tyrosine kinases 603Cytokine receptors and nonreceptor protein-tyrosine
kinases 606Receptors linked to other enzymatic activities 607
Pathways of Intracellular Signal Transduction 608
The cAMP pathway: second messengers and protein phosphorylation 608
Cyclic GMP 611Phospholipids and Ca2+ 612The PI 3-kinase/Akt and mTOR pathways 615MAP kinase pathways 617The JAK/STAT and TGF-b/Smad pathways 623NF-kB signaling 625The Hedgehog, Wnt, and Notch pathways 625
Signal Transduction and the Cytoskeleton 628
Integrins and signal transduction 628Signaling from cell adhesion molecules 630Regulation of the actin cytoskeleton 630
Signaling Networks 632Feedback and crosstalk 632
Networks of cellular signal transduction 634KEY EXPERIMENT
G Protein-Coupled Receptors and Odor Detection 601
MOLECULAR MEDICINE
Cancer: Signal Transduction and the ras Oncogenes 620
Summary and Key Terms 635Questions 637References and Further Reading 638
CHAPTER 16
The Cell Cycle 641The Eukaryotic Cell Cycle 641
Phases of the cell cycle 642Regulation of the cell cycle by cell growth and
extracellular signals 644Cell cycle checkpoints 646Restricting DNA replication to once per cell
cycle 647
Regulators of Cell Cycle Progression 647Protein kinases and cell cycle regulation 647Families of cyclins and cyclin-dependent
kinases 653Growth factors and the regulation of G1 Cdk’s 655DNA damage checkpoints 658
The Events of M Phase 659Stages of mitosis 659Entry into mitosis 662The spindle assembly checkpoint and progression
to anaphase 666
Part IV Cell Regulation 587
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xvi Contents
Cytokinesis 667
Meiosis and Fertilization 668The process of meiosis 668Regulation of oocyte meiosis 671Fertilization 673
KEY EXPERIMENT
The Discovery of MPF 649KEY EXPERIMENT
The Identification of Cyclin 652
Summary and Key Terms 675Questions 677References and Further Reading 677
CHAPTER 17
Cell Death and Cell Renewal 681Programmed Cell Death 681
The events of apoptosis 682Caspases: the executioners of apoptosis 685Central regulators of apoptosis: the Bcl-2
family 686Signaling pathways that regulate apoptosis 689Alternative pathways of programmed cell death 692
Stem Cells and the Maintenance of Adult Tissues 692
Proliferation of differentiated cells 693Stem cells 695Medical applications of adult stem cells 701
Pluripotent Stem Cells, Cellular Reprogramming, and Regenerative Medicine 703
Embryonic stem cells 704Somatic cell nuclear transfer 705Induced pluripotent stem cells 707Transdifferentiation of somatic cells 708
KEY EXPERIMENT
Identification of Genes Required for Programmed Cell Death 684
KEY EXPERIMENT
Culture of Embryonic Stem Cells 702
Summary and Key Terms 708Questions 710References and Further Reading 710
CHAPTER 18
Cancer 713The Development and Causes of
Cancer 713Types of cancer 713The development of cancer 715Causes of cancer 717Properties of cancer cells 718Transformation of cells in culture 722
Tumor Viruses 723Hepatitis B and C viruses 723Small DNA tumor viruses 724Herpesviruses 726Retroviruses 726
Oncogenes 727Retroviral oncogenes 727Proto-oncogenes 728Oncogenes in human cancer 731Functions of oncogene products 735
Tumor Suppressor Genes 741Identification of tumor suppressor genes 741Functions of tumor suppressor gene products 745Roles of oncogenes and tumor suppressor genes in
tumor development 748
Molecular Approaches to Cancer Treatment 749
Prevention and early detection 749Treatment 750
KEY EXPERIMENT
The Discovery of Proto-Oncogenes 730MOLECULAR MEDICINE
Imatinib: Cancer Treatment Targeted against the bcr/abl Oncogene 752
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Contents xvii
Summary and Key Terms 755Questions 757References and Further Reading 757Answers to Questions 761
Glossary 773Illustration Credits 797Index 799
©2013 Sinauer Associates, Inc. This material cannot be copied, reproduced, manufacturedor disseminated in any form without express written permission from the publisher.