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.
Brief Contents

PART I PART III

Introduction 1 Cell Structure and Function 343
Chapter 1 An Overview of Cells Chapter 9 The Nucleus 345
and Cell Research 3
Chapter 10 Protein Sorting and
Chapter 2 The Composition of Cells 43 Transport 373

Chapter 3 Cell Metabolism 73 Chapter 11 Bioenergetics and

Metabolism 421
Chapter 4 Fundamentals of
Molecular Biology 103 Chapter 12 The Cytoskeleton and
Cell Movement 459
PART II Chapter 13 The Plasma Membrane 515
The Flow of Genetic
Information 151 Chapter 14 Cell Walls, the Extracellular
Matrix, and Cell
Chapter 5 The Organization and Sequences Interactions 557
of Cellular Genomes 153

Chapter 6 Replication, Maintenance, and

PART IV
Rearrangements of Genomic Cell Regulation 587
DNA 191
Chapter 15 Cell Signaling 589
Chapter 7 RNA Synthesis and
Processing 239 Chapter 16 The Cell Cycle 641

Chapter 8 Protein Synthesis, Chapter 17 Cell Death and Cell

Processing, and Regulation 297 Renewal 681

Chapter 18 Cancer 713

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Contents
Preface 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 3
The Origin and Evolution of Cells 4
Summary and Key Terms 39
The first cell 4
The evolution of metabolism 6 Questions 40
Present-day prokaryotes 8 References and Further Reading 41
Eukaryotic cells 9
The origin of eukaryotes 10 CHAPTER 2
The development of multicellular organisms 13
Cells as Experimental Models 17 The Composition of
E. coli 17 Cells 43
Yeasts 18
Caenorhabditis elegans 18 The Molecules of Cells 43
Drosophila melanogaster 19 Carbohydrates 44
Arabidopsis thaliana 19 Lipids 46
Vertebrates 20 Nucleic acids 49
Tools of Cell Biology 22 Proteins 52
Light microscopy 22 Cell Membranes 58
Electron microscopy 28 Membrane lipids 58
Subcellular fractionation 31 Membrane proteins 59
Growth of animal cells in culture 32 Transport across cell membranes 62
Culture of plant cells 36
Viruses 36
Proteomics: Large-Scale Analysis of Cell
Proteins 65
KEY EXPERIMENT
Identification of cell proteins 65
Animal Cell Culture 34
Global analysis of protein localization 67
MOLECULAR MEDICINE Protein interactions 68
Viruses and Cancer 37

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 Contents ix

KEY EXPERIMENT CHAPTER 4

The Folding of Polypeptide Chains 54
KEY EXPERIMENT Fundamentals of
The Structure of Cell Membranes 62
Summary and Key Terms 70
Molecular Biology 103
Questions 71 Heredity, Genes, and DNA 103
References and Further Reading 71 Genes and chromosomes 103
Genes and enzymes 105
CHAPTER 3 Identification of DNA as the genetic material 107
The structure of DNA 108
Cell Metabolism 73 Replication of DNA 109
Expression of Genetic Information 110
The Central Role of Enzymes as Biological Colinearity of genes and proteins 111
Catalysts 73 The role of messenger RNA 112
The catalytic activity of enzymes 73 The genetic code 113
Mechanisms of enzymatic catalysis 74 RNA viruses and reverse transcription 115
Coenzymes 76
Regulation of enzyme activity 79
Recombinant DNA 118
Restriction endonucleases 118
Metabolic Energy 81 Generation of recombinant DNA molecules 120
Free energy and ATP 81 Vectors for recombinant DNA 122
The generation of ATP from glucose 84 DNA sequencing 124
The derivation of energy from other organic Expression of cloned genes 126
molecules 89
Photosynthesis 90 Detection of Nucleic Acids and Proteins 127
Amplification of DNA by the polymerase chain
The Biosynthesis of Cell Constituents 91 reaction 127
Carbohydrates 92 Nucleic acid hybridization 129
Lipids 93 Antibodies as probes for proteins 132
Proteins 94
Nucleic acids 98
Gene Function in Eukaryotes 135
Genetic analysis in yeasts 135
KEY EXPERIMENT
Gene transfer in plants and animals 136
Antimetabolites and Chemotherapy 97
Mutagenesis of cloned DNAs 139
MOLECULAR MEDICINE Introducing mutations into cellular genes 140
Phenylketonuria 98 Interfering with cellular gene expression 142
Summary and Key Terms 99 KEY EXPERIMENT
Questions 100 The DNA Provirus Hypothesis 117
References and Further Reading 101 KEY EXPERIMENT
RNA Interference 144
Summary and Key Terms 146
Questions 148
References and Further Reading 148

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x Contents

Part II The Flow of

Genetic Information 151
CHAPTER 5
The Organization and
Sequences of Cellular
Genomes 153
CHAPTER 6
The Complexity of Eukaryotic Genomes 153
Introns and exons 155 Replication, Maintenance,
Repetitive DNA sequences 159
Gene duplication and pseudogenes 161 and Rearrangements
The Sequences of Complete Genomes 162 of Genomic DNA 191
The genomes of bacteria and yeast 163
The genomes of Caenorhabditis elegans, Drosophila
DNA Replication 191
melanogaster, and other invertebrates 165 DNA polymerases 192
Plant genomes 166 The replication fork 193
The human genome 166 The fidelity of replication 200
The genomes of other vertebrates 169 Origins and the initiation of replication 201
Telomeres and telomerase: maintaining the
Chromosomes and Chromatin 171 ends of chromosomes 205
Chromatin 172
Centromeres 176
DNA Repair 207
Telomeres 180 Direct reversal of DNA damage 208
Excision repair 210
Bioinformatics and Systems Biology 181 Base-excision repair 210
Systematic screens of gene function 181 Nucleotide-excision repair 210
Regulation of gene expression 182 Transcription-coupled repair 213
Variation among individuals and genomic Mismatch repair 213
medicine 184 Translesion DNA synthesis 216
KEY EXPERIMENT Repair of double-strand breaks 216
The Discovery of Introns 156
DNA Rearrangements 219
KEY EXPERIMENT
Site-specific recombination 219
The Human Genome 167 Transposition via DNA intermediates 227
Summary and Key Terms 186 Transposition via RNA intermediates 228
Questions 187 Gene amplification 232
References and Further Reading 188 MOLECULAR MEDICINE
Colon Cancer and DNA Repair 215
KEY EXPERIMENT
Rearrangement of Immunoglobulin Genes 220

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 Contents xi

Summary and Key Terms 233 KEY EXPERIMENT

Questions 235 Isolation of a Eukaryotic Transcription Factor 259
References and Further Reading 236 KEY EXPERIMENT
The Discovery of snRNPs 284
CHAPTER 7 Summary and Key Terms 291
Questions 293
RNA Synthesis and References and Further Reading 294
Processing 239
CHAPTER 8
Transcription in Prokaryotes 239
RNA polymerase and transcription 240 Protein Synthesis,
Repressors and negative control of
transcription 243
Processing, and
Positive control of transcription 245 Regulation 297
Eukaryotic RNA Polymerases and General
Transcription Factors 245 Translation of mRNA 297
Eukaryotic RNA polymerases 246 Transfer RNAs 298
General transcription factors and initiation The ribosome 299
of transcription by RNA polymerase II 246 The organization of mRNAs and the initiation of
Transcription by RNA polymerases I and III 250 translation 305
The process of translation 307
Regulation of Transcription in Regulation of translation 313
Eukaryotes 251
Protein Folding and Processing 319
cis-acting regulatory sequences: promoters and
enhancers 251 Chaperones and protein folding 319
Transcription factor binding sites 255 Enzymes that catalyze protein folding 322
Transcriptional regulatory proteins 258 Protein cleavage 323
Structure and function of transcriptional Glycosylation 325
activators 260 Attachment of lipids 327
Eukaryotic repressors 263 Regulation of Protein Function 329
Regulation of elongation 264 Regulation by small molecules 329
Relationship of chromatin structure to Protein phosphorylation and other
transcription 266 modifications 330
Regulation of transcription by noncoding RNAs 271 Protein-protein interactions 335
DNA methylation 273
Protein Degradation 335
RNA Processing and Turnover 275 The ubiquitin-proteasome pathway 335
Processing of ribosomal and transfer RNAs 275 Lysosomal proteolysis 338
Processing of mRNA in eukaryotes 277 KEY EXPERIMENT
Splicing mechanisms 279 Catalytic Role of Ribosomal RNA 304
Alternative splicing 286
KEY EXPERIMENT
RNA editing 288
RNA degradation 289 The Discovery of Protein-Tyrosine Kinases 333
Summary and Key Terms 339
Questions 340
References and Further Reading 341

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xii Contents

Part III Cell Structure

and Function 343
CHAPTER 9
The Nucleus 345
The Nuclear Envelope and Traffic between
the Nucleus and the Cytoplasm 345 CHAPTER 10
Structure of the nuclear envelope 346
The nuclear pore complex 350 Protein Sorting and
Selective transport of proteins to and from the
nucleus 353
Transport 373
Regulation of nuclear protein import 356 The Endoplasmic Reticulum 373
Transport of RNAs 357
The endoplasmic reticulum and protein
Internal Organization of the Nucleus 359 secretion 374
Chromosome organization and gene expression 359 Targeting proteins to the endoplasmic reticulum 376
Sub-compartments within the nucleus 362 Insertion of proteins into the ER membrane 381
The Nucleolus and rRNA Processing 365 Protein folding and processing in the ER 386
Quality control in the ER 389
Ribosomal RNA genes and the organization of the
nucleolus 365 The smooth ER and lipid synthesis 392
Transcription and processing of rRNA 367 Export of proteins and lipids from the ER 395
Ribosome assembly 368 The Golgi Apparatus 398
Additional functions of the nucleolus 369 Organization of the Golgi 398
MOLECULAR MEDICINE Protein glycosylation within the Golgi 400
Nuclear Lamina Diseases 348 Lipid and polysaccharide metabolism in the
KEY EXPERIMENT Golgi 402
Identification of Nuclear Localization Signals 352 Protein sorting and export from the Golgi
apparatus 403
Summary and Key Terms 370
Questions 371
The Mechanism of Vesicular Transport 406
Experimental approaches to understanding vesicular
References and Further Reading 372 transport 406
Cargo selection, coat proteins, and
vesicle budding 407
Vesicle fusion 410
Lysosomes 412
Lysosomal acid hydrolases 412
Endocytosis and lysosome formation 414
Phagocytosis and autophagy 416

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 Contents xiii

KEY EXPERIMENT Questions 457

The Signal Hypothesis 378 References and Further Reading 458
MOLECULAR MEDICINE
Gaucher Disease 413 CHAPTER 12
Summary and Key Terms 417
Questions 419 The Cytoskeleton and
References and Further Reading 419 Cell Movement 459
CHAPTER 11 Structure and Organization of Actin
Filaments 459
Bioenergetics and Assembly and disassembly of actin filaments 460
Organization of actin filaments 465
Metabolism 421 Association of actin filaments with the plasma
membrane 467
Mitochondria 421 Protrusions of the cell surface 471
Organization and function of mitochondria 422
The genetic system of mitochondria 424
Actin, Myosin, and Cell Movement 472
Protein import and mitochondrial assembly 425 Muscle contraction 473
Contractile assemblies of actin and myosin in
The Mechanism of Oxidative nonmuscle cells 477
Phosphorylation 431 Unconventional myosins 479
The electron transport chain 431 Formation of protrusions and cell movement 480
Chemiosmotic coupling 432
Microtubules 482
Transport of metabolites across the inner
membrane 436 Structure and dynamic organization of
microtubules 482
Chloroplasts and Other Plastids 438 Assembly of microtubules 485
The structure and function of chloroplasts 438 Organization of microtubules within cells 488
The chloroplast genome 440
Microtubule Motors and Movement 490
Import and sorting of chloroplast proteins 441
Other plastids 444 Identification of microtubule motor proteins 490
Cargo transport and intracellular organization 493
Photosynthesis 446 Cilia and flagella 496
Electron transport 446 Reorganization of microtubules during mitosis 499
ATP synthesis 449 Chromosome movement 500
Peroxisomes 450 Intermediate Filaments 502
Functions of peroxisomes 451 Intermediate filament proteins 502
Peroxisome assembly 453 Assembly of intermediate filaments 504
MOLECULAR MEDICINE Intracellular organization of intermediate
Diseases of Mitochondria: filaments 505
Leber’s Hereditary Optic Neuropathy 426 Functions of intermediate filaments: keratins and
KEY EXPERIMENT diseases of the skin 507
The Chemiosmotic Theory 434 KEY EXPERIMENT

Summary and Key Terms 455 The Isolation of Kinesin 491

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xiv Contents

KEY EXPERIMENT CHAPTER 14

Expression of Mutant Keratin
Causes Abnormal Skin Development 508
Cell Walls, the Extracellular
Summary and Key Terms 510
Questions 512
Matrix, and Cell
References and Further Reading 512 Interactions 557
CHAPTER 13 Cell Walls 557
Bacterial cell walls 557
The Plasma Membrane 515 Eukaryotic cell walls 557
The Extracellular Matrix and Cell-Matrix
Structure of the Plasma Membrane 515 Interactions 564
The phospholipid bilayer 515 Matrix structural proteins 564
Membrane proteins 519 Matrix polysaccharides 568
Mobility of membrane proteins 524 Matrix adhesion proteins 569
The glycocalyx 525 Cell-matrix interactions 571
Transport of Small Molecules 526 Cell-Cell Interactions 574
Passive diffusion 526 Adhesion junctions 574
Facilitated diffusion and carrier proteins 527 Tight junctions 577
Ion channels 529 Gap junctions 578
Active transport driven by ATP hydrolysis 537 Plasmodesmata 581
Active transport driven by ion gradients 540 KEY EXPERIMENT
Endocytosis 544 The Characterization of Integrin 572
Phagocytosis 544 MOLECULAR MEDICINE
Receptor-mediated endocytosis 545 Gap Junction Diseases 580
Protein trafficking in endocytosis 550 Summary and Key Terms 582
MOLECULAR MEDICINE
Questions 583
Cystic Fibrosis 541
References and Further Reading 584
KEY EXPERIMENT
The LDL Receptor 548
Summary and Key Terms 553
Questions 554
References and Further Reading 555

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 Part IV Cell Regulation 587

Contents xv

Part IV Cell
Regulation 587
CHAPTER 15
Cell Signaling 589
Signaling Molecules and Their
Receptors 589 Networks of cellular signal transduction 634
KEY EXPERIMENT
Modes of cell-cell signaling 590
Steroid hormones and the nuclear receptor G Protein-Coupled Receptors and Odor
superfamily 591 Detection 601
Nitric oxide and carbon monoxide 593 MOLECULAR MEDICINE
Neurotransmitters 594 Cancer: Signal Transduction
Peptide hormones and growth factors 594 and the ras Oncogenes 620
Eicosanoids 596 Summary and Key Terms 635
Plant hormones 598 Questions 637
Functions of Cell Surface Receptors 599 References and Further Reading 638
G protein-coupled receptors 600
Receptor protein-tyrosine kinases 603 CHAPTER 16
Cytokine receptors and nonreceptor protein-tyrosine
kinases 606 The Cell Cycle 641
Receptors linked to other enzymatic activities 607
Pathways of Intracellular Signal The Eukaryotic Cell Cycle 641
Transduction 608 Phases of the cell cycle 642
The cAMP pathway: second messengers and protein Regulation of the cell cycle by cell growth and
phosphorylation 608 extracellular signals 644
Cyclic GMP 611 Cell cycle checkpoints 646
Phospholipids and Ca2+ 612 Restricting DNA replication to once per cell
The PI 3-kinase/Akt and mTOR pathways 615 cycle 647
MAP kinase pathways 617 Regulators of Cell Cycle Progression 647
The JAK/STAT and TGF-b/Smad pathways 623 Protein kinases and cell cycle regulation 647
NF-kB signaling 625 Families of cyclins and cyclin-dependent
The Hedgehog, Wnt, and Notch pathways 625 kinases 653
Signal Transduction and the Growth factors and the regulation of G1 Cdk’s 655
Cytoskeleton 628 DNA damage checkpoints 658
Integrins and signal transduction 628 The Events of M Phase 659
Signaling from cell adhesion molecules 630 Stages of mitosis 659
Regulation of the actin cytoskeleton 630 Entry into mitosis 662
Signaling Networks 632 The spindle assembly checkpoint and progression
to anaphase 666
Feedback and crosstalk 632

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xvi Contents

Cytokinesis 667 KEY EXPERIMENT

Meiosis and Fertilization 668 Culture of Embryonic Stem Cells 702
The process of meiosis 668 Summary and Key Terms 708
Regulation of oocyte meiosis 671 Questions 710
Fertilization 673 References and Further Reading 710
KEY EXPERIMENT
The Discovery of MPF 649 CHAPTER 18
KEY EXPERIMENT
The Identification of Cyclin 652 Cancer 713
Summary and Key Terms 675
The Development and Causes of
Questions 677
Cancer 713
References and Further Reading 677 Types of cancer 713
The development of cancer 715
CHAPTER 17 Causes of cancer 717
Properties of cancer cells 718
Cell Death and Cell Transformation of cells in culture 722
Renewal 681 Tumor Viruses 723
Hepatitis B and C viruses 723
Programmed Cell Death 681 Small DNA tumor viruses 724
The events of apoptosis 682 Herpesviruses 726
Caspases: the executioners of apoptosis 685 Retroviruses 726
Central regulators of apoptosis: the Bcl-2
family 686
Oncogenes 727
Signaling pathways that regulate apoptosis 689 Retroviral oncogenes 727
Alternative pathways of programmed cell death 692 Proto-oncogenes 728
Oncogenes in human cancer 731
Stem Cells and the Maintenance of Adult Functions of oncogene products 735
Tissues 692
Proliferation of differentiated cells 693
Tumor Suppressor Genes 741
Stem cells 695 Identification of tumor suppressor genes 741
Medical applications of adult stem cells 701 Functions of tumor suppressor gene products 745
Roles of oncogenes and tumor suppressor genes in
Pluripotent Stem Cells, Cellular tumor development 748
Reprogramming, and
Regenerative Medicine 703 Molecular Approaches to Cancer
Treatment 749
Embryonic stem cells 704
Somatic cell nuclear transfer 705 Prevention and early detection 749
Induced pluripotent stem cells 707 Treatment 750
Transdifferentiation of somatic cells 708 KEY EXPERIMENT
KEY EXPERIMENT
The Discovery of Proto-Oncogenes 730
Identification of Genes Required MOLECULAR MEDICINE
for Programmed Cell Death 684 Imatinib: Cancer Treatment Targeted
against the bcr/abl Oncogene 752

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 Contents xvii

Summary and Key Terms 755 Glossary 773

Questions 757 Illustration Credits 797
References and Further Reading 757
Index 799
Answers to Questions 761

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or disseminated in any form without express written permission from the publisher.