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    T H E C E L L

    Fifth Edition

    GEOFFREY M . COOPER • ROBERT E. HAUSM AN

    Boston University

    ASM PRESS

    Washington, D.C.

    1

    SINAUER ASSOCIATES, INC.

    Sunderland, Massachusetts

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      r i e f C o n t e n t s

    PARTI

      Introduction 1

    C h a p t e r

      1

      A n O v e r v i e w o f C e l ls a n d C e l l R e s e a rc h   3

    C h a p te r 2 T h e C o m p o s i t i o n o f C e l ls  43

    C h a p te r 3 C e l l M e t a b o l i s m  73

    C h a p te r 4 F u n d a m e n t a l s o f M o l e c u l a r B io l o g y 1 0 3

    P R T   I I  The Flow of Genetic Inform ation 153

    C h a p te r 5 T h e O r g a n i z a t i o n a n d S e q u e n c e s o f C e l lu l a r G e n o m e s 1 5 5

    C h a p te r 6 R e p l ic a t io n M a i n t e n a n c e a n d R e a r r a n g e m e n t s o f G e n o m i c D N A 2 0 1

    C h a p te r 7 R N A S y n t h e s i s a n d P r o c e s s in g  251

    C h a p te r 8 P r o t e i n S y n t h e s i s P r o c e s s i n g a n d R e g u l a t io n   309

    P R T   I I I  Cell Structure and Function 353

    C h a p te r 9 T h e N u c le u s 3 5 5

    C h a p te r 1 0 P r o t e in S o r t in g a n d T r a n s p o r t :

    T h e E n d o p l a s m ic R e t i c u l u m G o l g i A p p a r a t u s a n d L y s o s o m e s 3 8 3

    C h a p t e r

      1 1

      B i o e n e r g e t ic s a n d M e t a b o l i s m :

    M i t o c h o n d r i a C h l o r o p la s t s a n d P e r o x is o m e s 4 3 3

    C h a p te r 1 2 T h e C y t o s k e l e to n a n d C e l l M o v e m e n t 4 7 3

    C h a p te r 1 3 T h e P la s m a M e m b r a n e 5 2 9

    C h a p te r 1 4 C e l l W a l ls t h e E x t ra c e l lu l a r M a t r i x a n d C e l l I n t e r a c t i o n s 5 7 1

    P R T   I V  Cell Regulation 601

    C h a p te r 1 5 C e l l S ig n a l in g 6 0 3

    C h a p te r 1 6 T h e C e l l C y c l e 6 5 3

    C h a p te r 1 7 C e l l D e a t h a n d C e l l R e n e w a l 6 9 3

    C h a p te r 1 8 C a n c e r 7 2 5

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    Features of  h e  ell xv

    lements to Accomp any The Cell xvii

    PART I INTRODUCTION

    An Overview of Cells

    and Cell Research

     3

    t Cell 4

    ution of Metabolism 6

    ukaryotic Cells

     

    ryotes 9

    Multicellular

    Organisms 12

     18

      18

      thaliana  19

    s of Cell Bio logy 21

    on Microsc opy 28

    owth of Anim al Cells in Culture 33

    lture of Plant Cells 36

    Animal Cell Culture 34

    Viruses and Cancer 37

    Summ ary and

      K ey  Terms

     39

    Questions

     41

    R efer ences a n d  F ur ther R ead ing  42

    2

    The Composition

    of Cells

     43

    The Molecules

    of Cells 43

    Carbohydrates 44

    Lipids 46

    Nucleic Acids 49

    Proteins 52

    Cell Me mbrane s 58

    Membrane Lipids 58

    Membrane Proteins 60

    Transport across Cell Mem branes 63

    Proteomics: Large-Scale

    An alysis of Cell Proteins 64

    Identifica tion of Cell Proteins 65

    Global Analysis of Protein

    Localization   67

    Protein Interactions 68

    KEY EXPERIMENT

    The Folding of Polypeptide Chains 54

    KEY EXPERIMENT

    The Structure of Cell Membranes 60

    Summ ary and

      K ey  Terms

     70

    Questions 71

    R efer ences

      a n d

      F ur ther R ead ing

      71

     

    Cell Metabolism

     73

    The Central Role of Enzymes as

    Biological Catalysts 73

    The Catalytic Activ ity of Enzymes 73

    Mechanisms of Enzymatic Catalysis 74

    Coenzymes 76

    Regulation of Enzyme Activity  79

    Me tabolic Energy 81

    Free Energy and ATP 81

    The Generation of

     ATP

      from

    Glucose 84

    The Derivation of Energy from Other

    Organic Molecules 89

    Photosynthesis 89

    The Biosynthesis of Cell

    Consti tuents 91

    Carbohydrates 92

    Lipids 93

    Proteins 94

    Nucleic Acids 96

    MOLECULAR MEDICINE

    Phenylketonuria 97

    KEY EXPERIMENT

    Antimetabolites and Chemotherapy 98

    Summ ary and

      K ey

     Terms  99

    Questions 100

    R efer ences a n d  F ur ther R ead ing

      1 1

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    VIM CONTENTS

    DNA Repair 216

    Direct Reversal of DNA Damage 216

    Excision Repair 219

    Translesion DNA Synthesis 224

    Repair of Doub le-Strand Breaks 226

    Recomb ination b etween

    Homologous DNA

    Sequences 227

    Models of Homologous

    Recombination 228

    Enzymes Involved in Homologous

    Recombination 229

    DNA Rearrangements 233

    Site-Specific Recombination 234

    Transposition via DNA

    Intermediates 240

    Transpos ition via RNA-

    Intermediates 242

    Gene Am plification 245

    MOLECULAR MEDICINE

    Colo n Cancer and DNA Repair 225

    KEY EXPERIMENT

    Rearrangement of Immunoglobulin

    Genes 236

    Summary and   e y Terms 247

    Que st ions 249

    References

     and Furthe r

     Reading

      24 9

    7

    R N A S y n t h e s is a n d

    P r o c e s s i n g   251

    Trans crip tion in

    Prokaryotes 251

    RNA Polymerase and Transcription 252

    Repressors and Negative Control of

    Transcription 256

    Positive Co ntro l of Transcription 258

    Eukaryotic RNA Polymerases

    and General Transcription

    Factors 258

    Eukaryotic RNA Polymerases 259

    General Transcription Factors and

    Initiation of Transcription by RNA

    Polymerase II 259

    Transcription by RNA Polymerases I

    and III 263

    Regulation of Transcription

    in Eukaryotes 265

    c/5-Acting Regulatory Sequences:

    Promoters and Enhancers 265

    Trans cription Factor Bind ing Sites 269

    Transcriptional Regulatory Proteins 270

    Structure and Function of

    Transcriptional Activators 273

    Eukaryotic Repressors 276

    Regulation of Elongation 278

    Relationship of Ch rom atin Structure to

    Transcription 278

    Regulation of Transcription by

    Noncoding RNAs 285

    DNA Methylation 286

    RNA Processing and

    Turnover 287

    Processing of Ribosomal and Transfer

    RNAs 288

    Processing of mRNA in Eukaryotes 290

    Splicing Mechanisms 293

    Alternative Splicing 298

    RNA Editing 300

    RNA Degrad ation 301

    KEY EXPERIMENT

    Isolation of a Eukaryotic Transcription

    Factor 272

    KEY EXPERIMENT

    The Discovery of snRNPs 294

    Summary and  e y  Terms 303

    Que st ions 305

    References and Further Reading  306

    8

    P r o t e i n S y n t h e s i s

    P r o c e s s i n g a n d

    R e g u l a t i o n   309

    Trans lation of mRNA 309

    Transfer RNAs 310

    TheRibosome 311

    The Organization of mRNAs and the

    Initiation of Translation 317

    The Process of Trans lation 318

    Regulation of Translation 323

    Protein Folding and

    Processing 329

    Chaperones and Protein Folding 330

    Enzymes tha t Catalyze Protein

    Folding 332

    Protein Cleavage 333

    Glycosylation 335

    Attac hm ent of Lipids 337

    Regulation of Protein

    Function 340

    Regulation by Small Molecules 340

    Protein Phospho rylation 341

    Protein-Protein Interactions 343

    Protein Degradation 345

    The Ubiquitin-Proteasome

    Pathway 345

    Lysosomal Proteolysis 348

    KEY EXPERIMENT

    Catalytic Role of Ribosomal RNA 316

    KEY EXPERIMENT

    The Discovery of Protein-Tyrosine

    Kinases 344

    Summ ary and  e y  Terms 34 9

    Que st ions 351

    References

     and Furthe r

     Reading

      35 1

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    CONTENTS

    IX

    PART

     III

      CELL STRUCTURE AND FUNCTION

    The Nucleus

      355

     and

     the

     Nucleus

    the Cytoplasm

     355

     of

      the Nuclear Envelope

      356

    ear Pore Com plex

      360

    ective Transport

     of

     Proteins

     to and

    from

     the

     Nucleus

      361

     of Nuclear Protein

    Import

      367

     of

     RNAs

     368

    ernal Org anization

     of

    Nucleus

     369

    Chromatin Structure

      370

     the

    Nucleus

     372

    e Nucleolus a nd rRNA

     374

     the

    Organization

     of

     the Nucleolus

      375

    of rRNA

     376

    osome Assembly

      378

    Nuclear Lamina Diseases  358

    Y EXPERIMENT

    Identification

     of

     Nuclear Localization

    Signals

     362

     and

     K e y Terms  379

      381

     and Furthe r Reading 381

    1

    1 1 Protein Sorting

    V

      and

      Transport:

    The Endoplasmic Reticulum

    Golgi Apparatus and

    Lysosomes 383

    The Endoplasmic

    Reticulum 383

    The Endoplasmic Reticulum

     and

     Protein

    Secretion

      384

    Targeting Proteins

     to the

     Endoplasmic

    Reticulum

      386

    Insertion

     of

     Proteins into

     the

      ER

    Membrane

      391

    Protein Folding

     and

     Processing

    in the

      ER  396

    Quality Control

     in the ER  398

    The Smooth

      ER

     and Lipid Synthesis

     402

    Export

     of

     Proteins and Lipids from

    th e

      ER 405

    The Golgi App aratus

      408

    Organization

     of

     the Golgi

      408

    Protein Glycosylation w ithin

    the Golgi

      410

    Lipid and Polysaccharide Metabolism

    in

     the

     Golgi

      412

    Protein So rting and Export from

     the

    Golgi A pparatus

      413

    The Mechanism

     of

     Vesicular

    Transport

      416

    Experimental Approaches

     to Under-

    stand ing Vesicular Transport

      416

    Cargo Selection, Coat Proteins,

     and

    Vesicle Bud ding

      418

    Vesicle Fusion

      420

    Lysosomes

     423

    Lysosomal Acid Hydrolases

      423

    Endocytosis and Lysosome Formation  426

    Phagocytosis and Au tophagy

      426

    KEY EXPERIMENT

    The Signal Hypothesis

      388

    MOLECULAR MEDICINE

    Caucher Disease  425

    Summary and

     K e y

     Terms  429

    Questions  431

    References and

     Furthe r

     Reading 431

    1

    1 Bioenergetics and

    I Metabolism:

    Mitochondria Chloroplasts

    and Peroxisomes 433

    Mitochondria 433

    Organization and Function

     of

    Mitochondria  434

    The Genetic System

     of

     M itochondria

      435

    Protein Import and Mitochondrial

    Assembly 437

    The Mechanism

     of

     O xidat ive

    Phosphorylat ion

      445

    The Electron Transport Chain

     445

    Chemiosmotic Cou pling

      446

    Transport

     of

     M etabolites across

     the

    Inner M embrane

      450

    Chloroplasts and Other

    Plastids

     452

    The Structure and F unction

    of Chloroplasts

      452

    The Chloroplast Genome

      454

    Imp ort and Sorting

     of

     Chloroplast

    Proteins

      455

    Othe r Plastids

     457

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    CONTENTS

    and II 460

    P Synthesis 46 4

    eroxisomes 464

    of Peroxisomes 465

    eroxisome Assembly 467

    Diseases of Mitochondria: Leber's

    Hereditary Optic Neuropathy 438

    EY EXPERIMENT

    The Chemiosmotic Theory 448

    umm ary and   K ey Terms 46 9

    Questions 471

    References

     and Further

     Reading

      47 1

    2

    The Cytoskeleton

    and Cell

    Movement 473

    Structure and Orga nization of

    Actin Filaments 473

    Assembly and Disassembly of Actin

    Filaments 474

    Organ ization of Actin Filaments 479

    Association of Actin Filaments with the

    Plasma Membrane 481

    Protrusions of the Ce ll Surface 485

    Act in, M yosin , and Cell

    Movement 487

    Muscle Contraction 487

    Contractile Assemblies of Actin and

    Myosin in Nonm uscle Cells 492

    Nonmuscle Myosins 493

    Formation of Protrusions and Cell

    Movement 494

    Intermediate Filaments 496

    Intermediate Filament Proteins 496

    ssembly of Intermediate Filaments 498

    Intracellular Organization of

    Intermediate Filaments 499

    Functions of Keratins and

    Ne urofilam ents: Diseases of the Skin

    and Nervous System 501

    Microtubules 504

    Structure and Dynamic Organization

    of Microtubules 504

    Assembly of Microtu bules 507

    Organization of Microtubules within

    Cells 509

    Microtubule Motors and

    Movement 511

    Identification of Microtubule Motor

    Proteins 511

    Cargo Transport and Intracellular

    Organization 515

    Cilia and Flagella 516

    Reorganization of Microtubules

    during Mitosis 519

    Chromosome Movem ent 520

    KEY EXPERIMENT

    Expression of Mutant Keratin Causes

    Abnormal Skin Development 502

    KEY EXPERIMENT

    The Isolation of Kinesin 512

    Summ ary and

      K ey Terms

      52 2

    Questions 525

    References and Furthe r Reading  52 5

     

    The Plasma

    Membrane

     529

    Structure of the Plasma

    Membrane 529

    The Phos pholipid Bilayer 529

    Membrane Proteins 533

    Mobility of Membrane Proteins 538

    The Glycocalyx 540

    Transport of Small

    Molecules 540

    Passive Diffus ion 541

    Facilitated Diffusion and Carrier

    Proteins 542

    Ion Channels 544

    Active Transport Driven by ATP

    Hydrolysis 551

    Active Transport Driven by Ion

    Gradients 555

    Endocytosis 557

    Phagocytosis 557

    Receptor-Mediated Endocytosis 558

    Protein Trafficking in Endocytosis 563

    MOLECULAR MEDICINE

    Cystic Fibrosis 554

    KEY EXPERIMENT

    The

     LDL

      Receptor 560

    Summ ary and

      K ey  Terms

     56 7

    Questions 568

    References

     and Furthe r

     Reading

      56 8

      4

    Cell Walls the

    Extracellular

    Matrix and Cell

    Interactions

     571

    Cell W alls 571

    Bacterial Cell Walls 571

    Eukaryotic Cell Walls 572

    The Extracel lular Matr ix and

    Cell-Matrix Interactions 577

    Matrix Structural Proteins 578

    Matrix Polysaccharides 581

    Ma trix Adhesion Proteins 582

    Cell-Matrix Interactions 583

    Cell-Cell Inte rac tions 587

    Adhesion junctions 587

    Tig ht Junctions 590

    Gap Junctions 591

    Plasmodesmata 595

    KEY EXPERIMENT

    The Characterization of Integrins 584

    MOLECULAR MEDICINE

    Gap Junction Diseases 594

    Summ ary and

      K ey  Terms

      59 6

    Questions 598

    References

      and Further

     Reading

      59 8

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    CONTENTS

    X I

    PART IV   CELL REGULATION

    k

      ell

     Signaling

      603

    Signaling Molecules and

    Their Receptors 603

    Modes of Cell-Cell Signaling 604

    Steroid Hormones and the Nuclear

    Receptor Superfamily 605

    Nitric O xide and C arbon

    Monoxide 607

    Neurotransmitters 608

    Peptide Hormones and Gro wth

    Factors 609

    Eicosanoids 610

    Plant Hormones 612

    Functions of Cell Surface

    Receptors 613

    G Protein-Coupled Receptors 613

    Receptor Protein-Tyrosine Kinases 615

    Cytokine Receptors and Non receptor

    Protein-Tyrosine Kinases 620

    Receptors Linked to Othe r Enzymatic

    Activities 620

    Pathways of Intracellular

    Signal Transduction 621

    The cAMP Pathway: Second Messengers

    and Protein Phospho rylation 622

    Cyclic GMP 624

    Phospholipids and Ca

    2+

      625

    The

     PI

     3-Kinase/Akt and mTOR

    Pathways 628

    MAP Kinase Pathways 630

    The JAK/STAT and TGF-/3/Smad

    Pathways 636

    NF-JCB Signaling

      637

    The Hedgehog, Wnt, and No tch

    Pathways 638

    Signal Transduction and

    the Cytoskeleton 641

    Integrins and Signal Transduction 641

    Regulation of the Actin

    Cytoskeleton 642

    Signaling Ne tworks 644

    Feedback and Crosstalk 644

    Networks of Cellular Signal

    Transduction 646

    KEY EXPERIMENT

    C Protein-Coupled Receptors and Odor

    Detection 616

    MOLECULAR MEDICINE

    Cancer: Signal Transduction and the

    rasOncogenes 633

    Summary and  K ey Terms  64 7

    Questions 650

    References

     and Further

     Reading

      65 0

    16

    T h e C e ll

    C y c l e

      653

    The Eukaryotic Cell

    Cycle 653

    Phases of the Cell Cycle 654

    Regulation of the Cell Cycle by Cell

    Grow th and Extracellular Signals 655

    Cell Cycle Checkpoints 657

    Restricting DNA Replication to Once

    per Cell Cycle 659

    Regulators of Cell Cycle

    Progression 659

    Protein Kinases and Cell Cycle

    Regulation 659

    Families of Cyclins and C yclin-

    Dependent Kinases 664

    Gro wth Factors and the Regulation

    of G, Cdk's 667

    DNA Damage Checkpoints 670

    The Events of M Phase 672

    Stages of Mitosis 672

    Cdk1

      /Cyclin B and Progression to

    Metaphase 675

    The Spindle Assembly C heckpoint and

    Progression to Anaphase 678

    Cytokinesis 680

    Meiosis and Fert i l izat ion 681

    The Process of Meiosis 681

    Regulation of Ooc yte Meiosis 684

    Fertilization 687

    KEY EXPERIMENT

    The Discovery of MPF  660

    KEY EXPERIMENT

    The Identification of Cyclin 663

    Summary and  K ey Terms  68 8

    Quest ions 690

    References and Furthe r Reading  69 1

      7

    C e ll D e a t h

     and

    C e l l R e n e w a l

     693

    Programmed Cell Death 693

    The Events of Apoptosis 694

    Caspases: The Executioners

    of Apoptosis 697

    Central Regulators of Apoptosis:

    The Bcl-2 Family 699

    Signaling Pathways that Regulate

    Apoptosis 701

    Alternative Pathways of Programmed

    Cell Death 705

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