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 KARP’S CELL AND MOLECULAR BIOLOGY
CONCEPTS AND EXPERIMENTS EIGHTH EDITION

JANET IWASA WALLACE MARSHALL

University of Utah University of California, San Francisco

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 Vice President & Director Petra Recter
Director Kevin Witt
Senior Acquisitions Editor Bonnie Roth
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Cover Photo Credit Janet Iwasa

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 About the Authors
JANET IWASA is a faculty member in the Biochemistry Department at the University of Utah.
She received her bachelor’s degree from Williams College and a Ph.D. in Cell Biology from
the University of California, San Francisco, where she first became interested in the visualiza-
tion of biological processes. As a postdoctoral fellow, she was awarded a fellowship from the
National Science Foundation to create a multimedia exhibit with Nobel Laureate Jack Szostak
(Harvard University) and the Museum of Science, Boston. She later joined Harvard Medical
School as a faculty member in the Department of Cell Biology, where she utilized visualization
tools to aid in scientific communication, exploration and outreach. Janet’s award‐winning
illustrations and animations have appeared in scientific journals including Nature, Science and
Cell, as well as in the New York Times.

WALLACE MARSHALL is Professor of Biochemistry and Biophysics at the University of

California San Francisco. A native Long‐Islander, he received his bachelor’s degrees in Electrical
Engineering and Biochemistry from the State University of New York at Stony Brook, and his
Ph.D. in Biochemistry from UC San Francisco, where he studied organization of chromosomes
within the nucleus with John Sedat. He then moved to Yale University for postdoctoral studies
with Joel Rosenbaum, where he became interested in questions of organelle size control and
cell organization, using cilia, flagella, and centrioles as model systems. In 2003, he joined the
faculty at UCSF where he continues to study questions of cellular organization in a variety of
model organisms including green algae, yeast, ciliates, and mammalian cells. In addition to his
cell biology research, Dr. Marshall teaches Human Metabolism for the UCSF School of Pharmacy,
Cell Biology for the UCSF Graduate Division, and runs a two week lab course on cell behavior.
In 2014, he served as Program Committee Chair organizing the annual meeting of the American
Society for Cell Biology. He is currently co‐director of the Physiology summer course at the
Marine Biological Laboratory in Woods Hole, Massachusetts.

ABOUT THE COVER

The cover image shows an illustration, created by Janet Iwasa, of an idealized mammalian cell with different subcel-
lular compartments highlighted and digitally rendered to appear as a paper cut-out. An interactive version of this
illustration can be viewed at the website of the Cell Image Library (http://cellimagelibrary.org), where the selection
of any compartment will allow the user to view microscopic images of that compartment taken from real cells.

Karp-ffirs.indd 5 11/21/2015 5:25:03 PM

 Preface to the Eighth Edition
For the past two decades, Dr. Gerald Karp has written Cell and Working on the 8th edition side by side with Dr. Karp has given
Molecular Biology: Concepts and Experiments. During this time, us renewed admiration for his writing and his ability to keep track
he has maintained a consistent focus on combining rigor with of the cutting edge in the full range of topics that comprise cell and
accessibility, so that even students without prior training in cell molecular biology. In this and future editions of Karp’s Cell and
biology, molecular biology, or biochemistry have been able to Molecular Biology: Concepts and Experiments, we are dedicated to
learn cell biology not just as a collection of facts but as a process carrying out Dr. Karp’s original mission of providing an interesting,
of discovery. The value of this approach is that the lessons modern and readable text that is grounded in the experimental
learned extend far beyond the field of cell biology, and provide a approach. We welcome your ideas and feedback as we continue our
way for students to learn how science works, how new experi- work on this text, so please feel free to get in touch.
ments can overturn previous dogmas, and how new techniques
can lead to groundbreaking discovery. This approach makes cell Janet Iwasa ([email protected])
biology come alive. Wallace Marshall ([email protected])
After seven editions, Dr. Karp is ready to move on to other
adventures. We are excited to take on the challenge of continuing
Dr. Karp’s unique approach to teaching cell biology, while continu-
ing to put students first. Our goal for this revision was to build WileyPLUS Learning Space connects the text to carefully-selected
upon Karp’s hallmark experimental approach by bringing in our media examples such as video, animations, and diagrams, and
own unique perspectives and harnessing today’s technology. With provides students a multitude of tools and content for self-study
our new Experimental Walkthrough feature, available in and practice. Instructors can customize their course content for
WileyPLUS Learning Space, students can see first-hand how key students, create online homework and quizzes, and have insight
experimental techniques are performed in the lab. These offer a into student activity through data analytics and reporting features.
mix of video, which show how researchers carry out experiments, To try it, visit http://www.wileypluslearningspace.com. Here are
and 3D animations that show a molecular-level view of how the some of the resources available in WileyPLUS Learning Space:
experiments work. These Walkthroughs provide context and a vis-
ual explanation that helps make these important experimental ● Experimental Walkthrough Videos
techniques more concrete. ● Quantitative Tutorial Videos
A solid understanding of quantitative concepts is becoming ● Cell View Animations
increasingly important within cell biology, but is an area that
● Video Library
many students struggle with. To address this issue, we have also
added another new video feature, called Quantitative Tutorials, ● Biology Basics Animations
to visually illustrate how to solve specific analytical questions at ● Instructor’s Manual by Joel Piperberg, Millersville University
the end of each chapter. The Quantitative Tutorial provides an ● Clicker Questions by Leocadia Paliulis, Bucknell University
accessible, student‐friendly review of basic mathematical concepts and Omar Quintero, University of Richmond
used within the context of a biological problem, and will expand
● Lecture PowerPoint Presentations by Edmund B. Rucker,
the available resources for quantitative and physical concepts
University of Kentucky
within this 8th edition.
One key feature of the past editions was to highlight how cell ● Testbank and Answer Key by Robert Seiser, Roosevelt University
biology impacts our daily lives, in terms of medicine and other
areas of society. The Human Perspectives sections highlight ACKNOWLEDGEMENTS
human interest stories to reinforce and review basic cell biology,
and also provide examples of how fundamental discoveries have Gerald Karp, who dedicated many years to carefully and thought-
progressed into clinical practice. We have expanded this feature fully writing and editing this text, has left a remarkable legacy that
so that now every chapter has at least one Human Perspectives we are grateful to inherit. In putting together this edition, we are
section. As part of this feature we report on the latest clinical tri- thankful for his insight, wisdom and advice that was always cheer-
als for various cell biology‐based therapies and drugs, a feature fully and generously provided to us.
that we hope will inspire students who are pursuing careers in We are grateful to many individuals at John Wiley & Sons
health sciences fields. In addition to the full Human Perspectives who made this edition possible. Kevin Witt brought us on board at
sections, each chapter is now introduced with a short “chapter the beginning stages and infused us with his enthusiasm for the
opener” designed to generate enthusiasm about the science in project. Bonnie Roth provided superb leadership, guidance and
each chapter through provocative issues or questions. We hope support throughout the writing and editing process. Carrie
that this will give our readers the opportunity to think more Thompson, Melissa Edwards, Beth Pearson, and Liz Baird helped
about the links between science, society, and our place in the to keep us on organized and on track with the text and the various
universe. media elements. Patty Donovan of SPI Global played a central role

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 in coordinating the production of the text, incorporating changes to Adam, Aki and Kenzo, and the lifelong encouragement of her vii
the text and numerous illustrations and images. Billy Ray led the parents, Kuni and Mieko.
team in obtaining new images used in this edition. Maureen Eide Wallace Marshall thanks his scientific mentors, Rolf Sternglanz,

PREFACE
skillfully designed the interior and front cover. John Sedat, and Joel Rosenbaum, for launching him in the direction
Janet Iwasa thanks Rob Savage, Dyche Mullins and Jack Szostak, that he went. He thanks his parents, Clifford and Adele Marshall for
for inspiring and guiding her along the path towards becoming a making him who he is. And he thanks his family, Jennifer and Wyeth,
biologist. Janet is particularly grateful for the support of her family, for continued inspiration and support.

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 viii

We also wish to thank all reviewers of this and previous editions:

PREFACE

STEVE ALAS DENNIS O. CLEGG REBECCA HEALD

California State Polytechnic University, University of California—Santa Barbara University of California, Berkeley
Pomona KATE COOPER ROBERT HELLING
RAVI ALLADA Loras College University of Michigan
Northwestern University RONALD H. COOPER MARK HENS
DEREK APPLEWHITE University of California—Los Angeles University of North Carolina, Greensboro
Reed College PHILIPPA D. DARBRE ARTHUR HORWICH
LINDA AMOS University of Reading Yale University School of Medicine
MRC Laboratory of Molecular Biology ROGER W. DAVENPORT JEN‐CHIH HSIEH
KARL J. AUFDERHEIDE University of Maryland State University of New York at Stony Brook
Texas A&M University SUSAN DESIMONE JOEL A. HUBERMAN
GERALD T. BABCOCK Middlebury College Roswell Park Cancer Institute
Michigan State University LINDA DEVEAUX GREGORY D. D. HURST
WILLIAM E. BALCH Idaho State University University College London
The Scripps Research Institute RICHARD E. DEARBORN KEN JACOBSON
KENNETH J. BALAZOVICH Albany College of Pharmacy University of North Carolina
University of Michigan BARRY J. DICKSON MARIE JANICKE
JAMES BARBER Research Institute of Molecular Pathology University at Buffalo—SUNY
Imperial College of Science— DAVID DOE MICHAEL JONZ
Wolfson Laboratories Westfield State College University of Ottawa
JOHN D. BELL ROBERT S. DOTSON ROLAND KAUNAS
Brigham Young University Tulane University Texas A&M University
WENDY A. BICKMORE JENNIFER A. DOUDNA HAIG H. KAZAZIAN, JR.
Medical Research Council, Yale University University of Pennsylvania
United Kingdom MICHAEL EDIDIN LAURA R. KELLER
ASHOK BIDWAI Johns Hopkins University Florida State University
West Virginia University EVAN E. EICHLER TOM KELLER
ALLAN BLAKE University of Washington Florida State University
Seton Hall University ARRI EISEN REBECCA KELLUM
MARTIN BOOTMAN Emory University University of Kentucky
Babraham Institute ROBERT FILLINGAME GREG M. KELLY
DAVID BOURGAIZE University of Wisconsin Medical School University of Western Ontario
Whittier College ORNA COHEN-FIX NEMAT O. KEYHANI
DANIEL BRANTON National Institute of Health, Laboratory University of Florida
Harvard University of Molecular and Cellular Biology KIM KIRBY
THOMAS R. BREEN JACEK GAERTIG University of Guelph
Southern Illinois University University of Georgia NANCY KLECKNER
SHARON K. BULLOCK BENJAMIN GLICK Harvard University
Virginia Commonwealth University The University of Chicago WERNER KÜHLBRANDT
RODERICK A. CAPALDI REGINALD HALABY Max‐Planck‐Institut fÜr Biophysik
University of Oregon Montclair State University JAMES LAKE
GORDON G. CARMICHAEL MICHAEL HAMPSEY University of California—Los Angeles
University of Connecticut Health Center University of Medicine and Dentistry CLAIRE M. LEONARD
RATNA CHAKRABARTI of New Jersey William Paterson University
University of Central Florida MICHAEL HARRINGTON ROBERT C. LIDDINGTON
KENT D. CHAPMAN University of Alberta Burnham Institute
University of North Texas MARCIA HARRISON FAITH LIEBL
K. H. ANDY CHOO Marshall University Southern Illinois University, Edwardsville
Royal Children’s Hospitals— R. SCOTT HAWLEY VISHWANATH R. LINGAPPA
The Murdoch Institute American Cancer Society Research Professor University of California—San Francisco

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 JEANNETTE M. LOUTSCH CHARLES PUTNAM ADRIANA STOICA ix
Arkansas State University University of Arizona Georgetown University
JON LOWRANCE DAVID REISMAN ANN STURTEVANT

PREFACE
Lipscomb University University of South Carolina University of Michigan‐Flint
MARGARET LYNCH DONNA RITCH COLLEEN TALBOT
Tufts University University of Wisconsin— California State Univerity,
CHARLES MALLERY Green Bay San Bernardino
University of Miami JOEL L. ROSENBAUM WILLIAM TERZAGHI
MICHAEL A. MCALEAR Yale University Wilkes University
Wesleyan University WOLFRAM SAENGER GISELLE THIBAUDEAU
ARDYTHE A. MCCRACKEN Freie Universitat Berlin Mississippi State University
University of Nevada—Reno SHIVENDRA V. SAHI JEFFREY L. TRAVIS
THOMAS MCKNIGHT Western Kentucky University University at Albany—SUNY
Texas A&M University JAMIE SANFORD PAUL TWIGG
JOANN MEERSCHAERT Ohio Northern University University of Nebraska‐Kearney
St. Cloud State University JOSHUA SANDQUIST NIGEL UNWIN
JOHN MENNINGER Grinnell College MRC Laboratory of Molecular Biology
University of Iowa PRASANNA SATPUTE‐KRISHNAN AJIT VARKI
KIRSTEN MONSEN National Institute of Health University of California—San Diego
Montclair State University INDER M. SAXENA JOSE VAZQUEZ
ANDREW NEWMAN University of Texas, Austin New York University
Cambridge University RANDY SCHEKMAN CLAIRE E. WALCZAK
MICHELLE MORITZ University of California—Berkeley Indiana University
University of California—San Francisco SANDRA SCHMID PAUL E. WANDA
ROBERT MORRIS The Scripps Research Institute Southern Illinois University,
Wheaton College TRINA SCHROER Edwardsville
ALAN NIGHORN Johns Hopkins University JENNIFER WATERS
University of Arizona TIM SCHUH Harvard University
ROBERT M. NISSEN St. Cloud State University CHRIS WATTERS
California State University, Los Angeles DAVID SCHULTZ Middlebury College
JONATHAN NUGENT University of Louisville ANDREW WEBBER
University of London ROD SCOTT Arizona State University
VERONICA C. NWOSU Wheaton College BEVERLY WENDLAND
North Carolina Central University KATIE SHANNON Johns Hopkins University
MIKE O’DONNELL University of North Carolina— GARY M. WESSEL
Rockefeller University Chapel Hill Brown University
GREG ODORIZZI JOEL B. SHEFFIELD ERIC V. WONG
University of Colorado, Boulder Temple University University of Louisville
LEOCADIA PALIULIS ERIC SHELDEN ANDREW WOOD
Bucknell University Washington State University Southern Illinois University
JAMES G. PATTON DENNIS SHEVLIN GARY YELLEN
Vanderbilt University College of New Jersey Harvard Medical School
HUGH R. B. PELHAM JEFF SINGER MASASUKE YOSHIDA
MRC Laboratory of Molecular Biology Portland State University Tokyo Institute of Technology
JONATHAN PINES ROGER D. SLOBODA DANIELA ZARNESCU
Wellcome/CRC Institute Dartmouth College University of Arizona
DEBRA PIRES HARRIETT E. SMITH‐SOMERVILLE JIANZHI ZHANG
University of California—Los Angeles University of Alabama University of Michigan
MITCH PRICE BRUCE STILLMAN ROBERT A. ZIMMERMAN
Pennsylvania State University Cold Spring Harbor Laboratory University of Massachusetts

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Karp-fpref.indd 10 11/21/2015 5:28:26 PM
 Contents

1 Introduction to the Study of Cell and Hydrophobic Interactions and van der Waals Forces
The Life-Supporting Properties of Water 37
36

Molecular Biology 1
2.4 Acids, Bases, and Buffers 38
1.1 The Discovery of Cells 2 2.5 The Nature of Biological Molecules 39
Microscopy 2
Functional Groups 40
Cell Theory 2
A Classification of Biological Molecules by Function 40
1.2 Basic Properties of Cells 3 2.6 Carbohydrates 42
Cells Are Highly Complex and Organized 3
The Structure of Simple Sugars 42
Cells Possess a Genetic Program and the Means
Stereoisomerism 42
to Use It 5
Linking Sugars Together 43
Cells Are Capable of Producing More of Themselves 5
Polysaccharides 44
Cells Acquire and Utilize Energy 5
Cells Carry Out a Variety of Chemical Reactions 6 2.7 Lipids 46
Cells Engage in Mechanical Activities 6 Fats 46
Cells Are Able to Respond to Stimuli 6 Steroids 47
Cells Are Capable of Self-Regulation 6 Phospholipids 47
Cells Evolve 7
2.8 Building Blocks of Proteins 48
1.3 Characteristics That Distinguish Prokaryotic The Structures of Amino Acids 49
and Eukaryotic Cells 8 The Properties of the Side Chains 50
1.4 Types of Prokaryotic Cells 13 2.9 Primary and Secondary Structures of Proteins 53
Domain Archaea and Domain Bacteria 13 Primary Structure 53
Prokaryotic Diversity 14 Secondary Structure 53
1.5 Types of Eukaryotic Cells 15 2.10 Tertiary Structure of Proteins 55
Cell Differentiation 15 Myoglobin: The First Globular Protein Whose Tertiary
Model Organisms 16 Structure Was Determined 56
1 .6 T HE HUM AN P E R S P E CTIVE: Tertiary Structure May Reveal Unexpected Similarities
The Prospect of Cell Replacement Therapy 17
between Proteins 56
Protein Domains 57
1.7 The Sizes of Cells and Their Components 21
Dynamic Changes within Proteins 58
1.8 Viruses and Viroids 23
2.11 Quaternary Structure of Proteins 58
1 .9 E X P E R IM E N TAL PAT HWAY S:
The Structure of Hemoglobin 59
The Origin of Eukaryotic Cells 26 Protein–Protein Interactions 59

2.12 Protein Folding 60

Dynamics of Protein Folding 60
2 The Chemical Basis of Life 31
The Role of Molecular Chaperones 62
2.1 Covalent Bonds 32 2.13 TH E H UMAN P ERSPECTI V E:
Polar and Nonpolar Molecules 33 Protein Misfolding Can Have Deadly Consequences 62
Ionization 33 2.14 EX P ERIMEN TAL PATHWAYS:
2 .2 T HE HUM AN P E R S P E CTIVE: Chaperones—Helping Proteins Reach Their Proper Folded
Do Free Radicals Cause Aging? 34 State 67

2.3 Noncovalent Bonds 35 2.15 Proteomics and Interactomics 71

Ionic Bonds: Attractions between Charged Atoms 35 Proteomics 71
Hydrogen Bonds 35 Interactomics 72

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 xii 2.16 Protein Engineering 73 3.13 Separating Catabolic and Anabolic
Production of Novel Proteins 74 Pathways 110
Structure-Based Drug Design 75 3.14 TH E H UMAN P ERSPECTI V E:
CONTENTS

Caloric Restriction and Longevity 111

2.17 Protein Adaptation and Evolution 76
2.18 Nucleic Acids 77
2.19 The Formation of Complex Macromolecular 4 The Structure and Function of the
Structures 79 Plasma Membrane 114
The Assembly of Tobacco Mosaic Virus Particles 79
The Assembly of Ribosomal Subunits 79 4.1 Introduction to the Plasma Membrane 115
An Overview of Membrane Functions 115
A Brief History of Studies on Plasma Membrane
3 Bioenergetics, Enzymes, Structure 116

and Metabolism 81 4.2 The Lipid Composition of Membranes 118

Membrane Lipids 119
3.1 The Laws of Thermodynamics 82 The Nature and Importance of the Lipid Bilayer 120
The First Law of Thermodynamics 82 The Asymmetry of Membrane Lipids 121
The Second Law of Thermodynamics 83
4.3 Membrane Carbohydrates 122
3.2 Free Energy 85
4.4 Membrane Proteins 123
Free-Energy Changes in Chemical Reactions 85
Integral Membrane Proteins 124
Free-Energy Changes in Metabolic Reactions 86
Peripheral Membrane Proteins 125
3.3 Coupling Endergonic and Exergonic Reactions 88 Lipid-Anchored Membrane Proteins 125
3.4 Equilibrium versus Steady-State 4.5 Studying the Structure and Properties of Integral
Metabolism 88 Membrane Proteins 126
3.5 Enzymes as Biological Catalysts 89 Identifying Transmembrane Domains 127
The Properties of Enzymes 90 Experimental Approaches to Identifying Conformational
Changes within an Integral Membrane Protein 128
Overcoming the Activation Energy Barrier 90
The Active Site 92 4.6 Membrane Lipids and Membrane Fluidity 130
3.6 Mechanisms of Enzyme Catalysis 93 The Importance of Membrane Fluidity 131
Maintaining Membrane Fluidity 131
Substrate Orientation 94
Lipid Rafts 131
Changing Substrate Reactivity 94
Inducing Strain in the Substrate 94 4.7 The Dynamic Nature of the Plasma
3.7 Enzyme Kinetics 97 Membrane 132
The Diffusion of Membrane Proteins after Cell Fusion 133
The Michaelis-Menten Model of Enzyme Kinetics 97
Restrictions on Protein and Lipid Mobility 133
Enzyme Inhibitors 98
3. 8 T HE HUM AN P E R S P E CT IV E: 4.8 The Red Blood Cell: An Example of Plasma
The Growing Problem of Antibiotic Resistance 100 Membrane Structure 137
3.9 An Overview of Metabolism 103 Integral Proteins of the Erythrocyte Membrane 137
The Erythrocyte Membrane Skeleton 137
Oxidation and Reduction: A Matter of Electrons 103
The Capture and Utilization of Energy 103 4.9 Solute Movement across Cell Membranes 139
3.10 Glycolysis and Fermentation 105 The Energetics of Solute Movement 139
Formation of an Electrochemical Gradient 140
ATP Production in Glycolysis 105
Anaerobic Oxidation of Pyruvate: The Process of 4.10 Diffusion through the Lipid Bilayer 140
Fermentation 108 Diffusion of Substances through Membranes 140
3.11 Reducing Power 109 The Diffusion of Water through Membranes 141

3.12 Metabolic Regulation 109 4.11 The Diffusion of Ions through Membranes 143
Altering Enzyme Activity by Covalent Modification 109 4.12 EX P ERIMEN TAL PATHWAYS:
Altering Enzyme Activity by Allosteric Modulation 110 The Acetylcholine Receptor 147

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 4.13 Facilitated Diffusion 151 5.9 Using the Proton Gradient 192 xiii
4.14 Active Transport 152 The Role of the Fo Portion of ATP Synthase in ATP
Synthesis 192
Primary Active Transport: Coupling Transport to ATP

CONTENTS
Other Roles for the Proton-Motive Force in Addition to ATP
Hydrolysis 152
Synthesis 193
Other Primary Ion Transport Systems 154
Using Light Energy to Actively Transport Ions 155 5.10 Peroxisomes 193
Secondary Active Transport (or Cotransport): Coupling 5.11 TH E H UMAN P ERSPECTI V E:
Transport to Existing Ion Gradients 155 Diseases that Result from Abnormal Mitochondrial or
4 .1 5 T HE HUM AN P E R S P E C TIVE: Peroxisomal Function 195
Defects in Ion Channels and Transporters as a Cause of Inherited
Disease 157

4.16 Membrane Potentials 159

6 Photosynthesis and the
The Resting Potential 159 Chloroplast 199
The Action Potential 160
6.1 The Origin of Photosynthesis 200
4.17 Propagation of Action Potentials as an 6.2 Chloroplast Structure 201
Impulse 161
6.3 An Overview of Photosynthetic Metabolism 202
4.18 Neurotransmission: Jumping the Synaptic
Cleft 162 6.4 The Absorption of Light 203
Actions of Drugs on Synapses 165 6.5 Coordinating the Action of Two Different
Synaptic Plasticity 165 Photosynthetic Systems 205
6.6 The Operations of Photosystem II and
Photosystem I 207
5 Aerobic Respiration
PSII Operations: Obtaining Electrons by
and the Mitochondrion 168 Splitting Water 207
PSI Operations: The Production of NADPH 210
5.1 Mitochondrial Structure and Function 169
Mitochondrial Membranes 170 6.7 An Overview of Photosynthetic Electron
The Mitochondrial Matrix 172 Transport 211
5.2 Aerobic Metabolism in the Mitochondrion 172 6.8 Photophosphorylation 212
The Tricarboxylic Acid (TCA) Cycle 173 6.9 Carbohydrate Synthesis in C3 Plants 213
The Importance of Reduced Coenzymes in the Redox Control 215
Formation of ATP 175 Photorespiration 216
5 .3 T HE HUM AN P E R S P E CTIVE: Peroxisomes and Photorespiration 217
The Role of Anaerobic and Aerobic Metabolism in Exercise 177
6.10 Carbohydrate Synthesis in C4 and CAM
5.4 Oxidative Phosphorylation in the Formation of Plants 218
ATP 178 6.11 TH E H UMAN P ERSPECTI V E:
Oxidation–Reduction Potentials 179 Global Warming and Carbon Sequestration 219
Electron Transport 180
Types of Electron Carriers 180

5.5 Electron-Transport Complexes 182 7 Interactions between Cells and their

Complex I (NADH Dehydrogenase) 184 Environment 222
Complex II (succinate dehydrogenase) 185
Complex III (cytochrome bc1) 185 7.1 Overview of Extracellular Interactions 223
Complex IV (cytochrome c oxidase) 185 7.2 The Extracellular Matrix 224
5.6 Establishment of a Proton-Motive Force 186 7.3 Components of the Extracellular Matrix 226
5.7 The Structure of ATP Synthase 187 Collagen 226
Proteoglycans 228
5.8 The Binding Change Mechanism of ATP
Fibronectin 229
Formation 189
Laminin 229
Components of the Binding Change Hypothesis 189
Evidence to Support the Binding Change Mechanism and 7.4 Dynamic Properties of the Extracellular
Rotary Catalysis 190 Matrix 231

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 xiv 7.5 Integrins 231 8.5 Membrane Biosynthesis in the Endoplasmic
7.6 Anchoring Cells to Their Substratum 234 Reticulum 271
Focal Adhesions 234 8.6 Glycosylation in the Rough Endoplasmic
CONTENTS

Hemidesmosomes 236 Reticulum 273

7.7 Interactions of Cells with Other Cells 237 8.7 Mechanisms That Ensure the Destruction of
Selectins 238 Misfolded Proteins 275
The Immunoglobulin Superfamily 239 8.8 ER to Golgi Vesicular Transport 276
Cadherins 239
8.9 The Golgi Complex 276
7. 8 T HE HUM AN P E R S P E CT IV E :
Glycosylation in the Golgi Complex 278
The Role of Cell Adhesion in Inflammation and Metastasis 241
The Movement of Materials through the Golgi
7.9 Adherens Junctions and Desmosomes 244 Complex 278

7.10 The Role of Cell-Adhesion Receptors in 8.10 Types of Vesicle Transport 280
Transmembrane Signaling 245 COPII-Coated Vesicles: Transporting Cargo from the ER to
the Golgi Complex 281
7.11 Tight Junctions: Sealing the Extracellular
COPI-Coated Vesicles: Transporting Escaped Proteins Back
Space 245
to the ER 284
7.12 Gap Junctions and Plasmodesmata: Mediating
8.11 Beyond the Golgi Complex: Sorting Proteins at
Intercellular Communication 247
the TGN 285
Gap Junctions 248
Sorting and Transport of Lysosomal Enzymes 285
Plasmodesmata 250
Sorting and Transport of Nonlysosomal Proteins 286
7. 13 E X P E R IM E N TAL PAT HWAYS:
8.12 TH E H UMAN P ERSPECTI V E:
The Role of Gap Junctions in Intercellular Communication 251
Disorders Resulting from Defects in Lysosomal Function 286
7.14 Cell Walls 254 8.13 Targeting Vesicles to a Particular
Compartment 288
8 Cytoplasmic Membrane Systems: 8.14 Exocytosis 290
Structure, Function, and Membrane 8.15 Lysosomes 291
Trafficking 257 8.16 Plant Cell Vacuoles 292
8.17 Endocytosis 293
8.1 An Overview of the Endomembrane System 258
Receptor-Mediated Endocytosis and the Role of
8.2 A Few Approaches to the Study of Coated Pits 294
Endomembranes 260 The Role of Phosphoinositides in the Regulation of
Insights Gained from Autoradiography 260 Coated Vesicles 296
Insights Gained from the Use of the Green Fluorescent 8.18 EX P ERIMEN TAL PATHWAYS:
Protein 260
Receptor‐Mediated Endocytosis 297
Insights Gained from the Analysis of Subcellular Fractions 262
Insights Gained from the Use 8.19 The Endocytic Pathway 300
of Cell-Free Systems 263 8.20 Phagocytosis 303
Insights Gained from the Study of Mutant Phenotypes 263
8.21 Posttranslational Uptake of Proteins by
8.3 The Endoplasmic Reticulum 265 Peroxisomes, Mitochondria, and
The Smooth Endoplasmic Reticulum 266 Chloroplasts 304
The Rough Endoplasmic Reticulum 267 Uptake of Proteins into Peroxisomes 304
8.4 Functions of the Rough Endoplasmic Uptake of Proteins into Mitochondria 304
Reticulum 268 Uptake of Proteins into Chloroplasts 306
Synthesis of Proteins on Membrane-Bound versus Free
Ribosomes 268
Synthesis of Secretory, Lysosomal, or Plant Vacuolar 9 The Cytoskeleton and
Proteins 268
Processing of Newly Synthesized Proteins in the Endoplasmic
Cell Motility 309
Reticulum 270
9.1 Overview of the Major Functions of the
Synthesis of Integral Membrane Proteins on ER-Bound
Ribosomes 270
Cytoskeleton 310

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 9.2 Structure and Function of Microtubules 311 10 The Nature of the Gene and the xv
Structure and Composition of Microtubules 312
Genome 366
Microtubule-Associated Proteins 313

CONTENTS
Microtubules as Structural Supports and Organizers 313 10.1 The Concept of a Gene as a Unit of
Microtubules as Agents of Intracellular Motility 314 Inheritance 367
9.3 Motor Proteins: Kinesins and Dyneins 315 10.2 The Discovery of Chromosomes 368
Motor Proteins Traverse the Microtubular Cytoskeleton 315
Kinesins 316 10.3 Chromosomes as the Carriers of Genetic
Cytoplasmic Dynein 317 Information 369
9 .4 E X P E R IM E N TAL PAT HWAY: 10.4 Genetic Analysis in Drosophila 370
The Step Size of Kinesin 319 Crossing Over and Recombination 371
9.5 Microtubule-Organizing Centers (MTOCs) 321 Mutagenesis and Giant Chromosomes 371
Centrosomes 321 10.5 The Structure of DNA 373
Basal Bodies and Other MTOCs 322
The Watson-Crick Proposal 374
Microtubule Nucleation 322
The Importance of the
9.6 Microtubule Dynamics 323 Watson-Crick Proposal 375
The Dynamic Properties of Microtubules 323 10.6 EX P ERIMEN TAL PATHWAYS:
The Underlying Basis of The Chemical Nature of the Gene 377
Microtubule Dynamics 325
10.7 DNA Supercoiling 381
9.7 Structure and Function of Cilia and Flagella 327
Structure of Cilia and Flagella 329 10.8 The Complexity of the Genome 382
Growth by Intraflagellar Transport 331 DNA Denaturation 383
The Mechanism of Ciliary DNA Renaturation 384
and Flagellar Locomotion 331
10.9 TH E H UMAN P ERSPECTI V E:
9 .8 T HE HUM AN P E R S P E CTIVE: Diseases That Result from Expansion of Trinucleotide
The Role of Cilia in Development and Disease 333 Repeats 387
9.9 Intermediate Filaments 335 10.10 The Stability of the Genome: Duplication 389
Intermediate Filament Assembly and Disassembly 335
Whole-Genome Duplication (Polyploidization) 389
Types and Functions of Intermediate Filaments 336
Duplication and Modification of DNA Sequences 390
9.10 Actin 338 Evolution of Globin Genes 390
Actin Structure 338
10.11 The Dynamic Nature of the Genome: “Jumping
Actin Filament Assembly and Disassembly 339
Genes” 391
9.11 Myosin: The Molecular Motor of Actin 341 Transposons 392
Conventional (Type II) Myosins 341 The Role of Mobile Genetic Elements in Genome
Unconventional Myosins 341 Evolution 393

9.12 Muscle Organization and Contraction 344 10.12 Sequencing Genomes: The Footprints of
Organization of Sarcomeres 346 Biological Evolution 394
The Sliding Filament Model
10.13 Comparative Genomics: “If It’s Conserved, It
of Muscle Contraction 346
Must Be Important” 396
9.13 Actin-Binding Proteins 351
10.14 The Genetic Basis of “Being Human” 397
9.14 Cellular Motility 353
9 .1 5 E X P E R IM E N TAL PAT HWAY:
10.15 Genetic Variation within the Human Species
Population 398
Studying Actin‐Based Motility without Cells 358
DNA Sequence Variation 398
9.16 Actin-dependent Processes During Structural Variation 399
Development 361 Copy Number Variation 399
Axonal Outgrowth 361
10.16 TH E H UMAN PERSPECTI V E:
9.17 The Bacterial Cytoskeleton 362 Application of Genomic Analyses to Medicine 400

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 xvi 11 The Central Dogma: DNA to RNA The Structure of tRNAs 439
tRNA Charging 441
to Protein 404
11.16 Translating Genetic Information: Initiation 442
CONTENTS

11.1 The Relationship between Genes, Proteins, Initiation of Translation in Prokaryotes 442
and RNAs 405 Initiation of Translation in Eukaryotes 443
Evidence That DNA Is the Genetic Material 405 The Role of the Ribosome 444
An Overview of the Flow of Information through the Cell 406
11.17 Translating Genetic Information: Elongation
11.2 The Role of RNA Polymerases in and Termination 445
Transcription 408 Elongation Step 1: Aminoacyl-tRNA Selection 445
11.3 An Overview of Transcription in Both Prokaryotic Elongation Step 2: Peptide Bond Formation 445
and Eukaryotic Cells 410 Elongation Step 3: Translocation 446
Elongation Step 4: Releasing the Deacylated tRNA 447
Transcription in Bacteria 410
Termination 448
Transcription and RNA Processing in Eukaryotic Cells 411

11.4 Synthesis and Processing of Eukaryotic 11.18 mRNA Surveillance and Quality Control 448

Ribosomal and Transfer RNAs 413 11.19 Polyribosomes 449

Synthesis and Processing of the rRNA Precursor 413 11.20 EX P ERIMEN TAL PATHWAYS:
The Role of snoRNAs in the Processing of Pre-rRNA 415 The Role of RNA as a Catalyst 450
Synthesis and Processing of the 5S rRNA 415
Transfer RNAs 416

11.5 Synthesis and Structure of Eukaryotic 12 Control of Gene Expression 455

Messenger RNAs 417
The Formation of Heterogeneous Nuclear RNA 12.1 Control of Gene Expression in Bacteria 456
(hnRNA) 417 Organization of Bacterial Genomes 456
The Machinery for mRNA Transcription 417 The Bacterial Operon 456
The Structure of mRNAs 419 Riboswitches 459
11.6 Split Genes: An Unexpected Finding 420 12.2 Structure of the Nuclear Envelope 460
11.7 The Processing of Eukaryotic Messenger The Nuclear Pore Complex and Its Role in
RNAs 423 Nucleocytoplasmic Trafficking 462
5′ Caps and 3′ Poly(A) Tails 423 RNA Transport 465
RNA Splicing: Removal of Introns from a Pre-RNA 425 12.3 Packaging the Eukaryotic Genome 465
11.8 Evolutionary Implications of Split Genes and Nucleosomes: The Lowest Level of Chromosome
RNA Splicing 429 Organization 465
Higher Levels of Chromatin Structure 467
11.9 Creating New Ribozymes in the Laboratory 429
12.4 Heterochromatin 469
11.10 RNA Interference 430
X Chromosome Inactivation 470
11. 11 T HE HUM AN P E R S P E CT IVE: The Histone Code and Formation of Heterochromatin 470
Clinical Applications of RNA Interference 432
12.5 The Structure of a Mitotic Chromosome 473
11.12 Small RNAs: miRNAs and piRNAs 433
Telomeres 473
miRNAs: A Class of Small RNAs that Regulate Gene Centromeres 477
Expression 434
12.6 TH E H UMAN P ERSPECTI V E:
piRNAs: A Class of Small RNAs that Function in Germ
Cells 435 Chromosomal Aberrations and Human Disorders 478

11.13 CRISPR and other Noncoding RNAs 435 12.7 Epigenetics: There’s More to Inheritance than
CRISPR: Noncoding RNA in Bacteria 435
DNA 480
Other Noncoding RNAs 436 12.8 The Nucleus as an Organized Organelle 480
11.14 Encoding Genetic Information 436 12.9 An Overview of Gene Regulation in
The Properties of the Genetic Code 436 Eukaryotes 483
Identifying the Codons 437 12.10 Profiling Gene Activity 485
11.15 Decoding the Codons: The Role of Transfer DNA Microarrays 485
RNAs 439 RNA Sequencing 487

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 12.11 The Role of Transcription Factors in Regulating 13.6 DNA Replication in Eukaryotic Cells 526 xvii
Gene Expression 488 Initiation of Replication in Eukaryotic Cells 526
12.12 The Structure of Transcription Factors 489 Restricting Replication to Once Per Cell Cycle 527

CONTENTS
The Eukaryotic Replication Fork 528
The Zinc-Finger Motif 490
Replication and Nuclear Structure 530
The Helix–Loop–Helix (HLH) Motif 490
The Leucine Zipper Motif 491 13.7 Chromatin Structure and Replication 530
12.13 DNA Sites Involved in Regulating 13.8 DNA Repair 531
Transcription 492 Nucleotide Excision Repair 532
12.14 An Example of Transcriptional Activation: Base Excision Repair 532
The Glucocorticoid Receptor 494 Mismatch Repair 534
Double-Strand Breakage Repair 534
12.15 Transcriptional Activation: The Role of
Enhancers, Promoters, and Coactivators 495 13.9 Between Replication and Repair 535
Coactivators That Interact with the Basal Transcription 13.10 TH E H UMAN PERSPECTI V E:
Machinery 496 Consequences of DNA Repair Deficiencies 536
Coactivators That Alter Chromatin Structure 496

12.16 Transcriptional Activation from Paused

Polymerases 499 14 Cell Division 539

12.17 Transcriptional Repression 499 14.1 The Cell Cycle 540

DNA Methylation 500 Phases of the Cell Cycle 540
Genomic Imprinting 501 Cell Cycles in Vivo 541
Long Noncoding RNAs (lncRNAs) as Transcriptional 14.2 Regulation of the Cell Cycle 542
Repressors 502
14.3 EX P ERIMEN TAL PATHWAYS:
12.18 RNA Processing Control 503 The Discovery and Characterization of MPF 543
12.19 Translational Control 505
14.4 Control of the Cell Cycle: The Role of Protein
Initiation of Translation 505 Kinases 546
Cytoplasmic Localization of mRNAs 506
Cyclin Binding 547
The Control of mRNA Stability 506
Cdk Phosphorylation/Dephosphorylation 547
12.20 The Role of MicroRNAs in Translational Cdk Inhibitors 548
Control 508 Controlled Proteolysis 548
Subcellular Localization 548
12.21 Posttranslational Control: Determining Protein
Stability 509 14.5 Control of the Cell Cycle: Checkpoints, Cdk
Inhibitors, and Cellular Responses 550
14.6 Overview of M Phase: Mitosis and
13 DNA Replication and Repair 512 Cytokinesis 552
13.1 DNA Replication 513 14.7 Prophase 552
Formation of the Mitotic Chromosome 552
13.2 DNA Replication in Bacterial Cells 516
Centromeres and Kinetochores 555
Replication Forks and Bidirectional Replication 517
Formation of the Mitotic Spindle 556
Unwinding the Duplex and Separating the Strands 517
The Dissolution of the Nuclear Envelope and Partitioning
The Properties of DNA Polymerases 518 of Cytoplasmic Organelles 558
Semidiscontinuous Replication 519
14.8 Prometaphase 559
13.3 The Machinery Operating at the Replication
Fork 521 14.9 Metaphase 560

14.10 Anaphase 562

13.4 The Structure and Functions of DNA
Polymerases 523 The Role of Proteolysis in Progression through Mitosis 562
The Events of Anaphase 564
Exonuclease Activities of DNA Polymerases 523
Forces Required for Chromosome Movements at
Ensuring High Fidelity during DNA Replication 523
Anaphase 564
13.5 Replication in Viruses 526 The Spindle Assembly Checkpoint 566

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 xviii 14.11 Telophase and Cytokinesis 567 15.11 The Ras-MAP Kinase Pathway 607
Motor Proteins Required for Mitotic Movements 567 Accessory Proteins 608
Cytokinesis 567 Adapting the MAP Kinase to Transmit Different Types of
CONTENTS

Cytokinesis in Plant Cells: Formation of the Cell Plate 570 Information 610

14.12 Overview of Meiosis 571 15.12 Signaling by the Insulin Receptor 611
The Insulin Receptor Is a Protein-Tyrosine Kinase 611
14.13 The Stages of Meiosis 574
Insulin Receptor Substrates 1 and 2 611
14. 14 T HE HUM AN P E R S P E CT IVE:
Glucose Transport 612
Meiotic Nondisjunction and Its Consequences 577
Diabetes Mellitus 613
14.15 Genetic Recombination during Meiosis 579 15.13 Signaling Pathways in Plants 613
15.14 The Role of Calcium as an Intracellular
15 Cell Signaling and Signal Messenger 613
Transduction: Communication IP3 and Voltage-Gated Ca2+ Channels 613
Visualizing Cytoplasmic Ca2+ Concentration in Living
between Cells 582 Cells 614
Ca2+-Binding Proteins 615
15.1 The Basic Elements of Cell Signaling
Regulating Calcium Concentrations in Plant Cells 617
Systems 583
15.15 Convergence, Divergence, and Cross-Talk
15.2 A Survey of Extracellular Messengers and Their
among Different Signaling Pathways 617
Receptors 586
15.16 The Role of NO as an Intercellular
15.3 Signal Transduction by G Protein-Coupled Messenger 619
Receptors 587 NO as an Activator of Guanylyl Cyclase 620
Receptors 587 Inhibiting Phosphodiesterase 620
G Proteins 588
Termination of the Response 589
15.17 Apoptosis (Programmed Cell Death) 621
Bacterial Toxins 590 The Extrinsic Pathway of Apoptosis 622
The Intrinsic Pathway of Apoptosis 623
15. 4 E X P E R IM E N TAL PAT HWAYS:
Necroptosis 624
The Discovery and Characterization of GTP‐Binding
Signaling Cell Survival 624
Proteins 590

15. 5 T HE HUM AN P E R S P E CT IV E:
Disorders Associated with G Protein‐Coupled Receptors 594 16 Cancer 627
15.6 Second Messengers 595
16.1 Basic Properties of a Cancer Cell 628
The Discovery of Cyclic AMP 595
Phosphatidylinositol-Derived Second Messengers 596 16.2 The Causes of Cancer 631
Phospholipase C 597 16.3 EX P ERIMEN TAL PATHWAYS:
15.7 The Specificity of G Protein-Coupled The Discovery of Oncogenes 632

Responses 599 16.4 Cancer: A Genetic Disorder 636

15.8 Regulation of Blood Glucose Levels 599 16.5 An Overview of Tumor-Suppressor Genes
Glucose Mobilization: An Example of a Response and Oncogenes 638
Induced by cAMP 600
16.6 Tumor-Suppressor Genes: The RB Gene 640
Signal Amplification 600
Other Aspects of cAMP Signal Transduction Pathways 600 16.7 Tumor-Suppressor Genes:
15.9 The Role of GPCRs in Sensory Perception 603 The TP53 Gene 642
The Role of p53: Guardian of the Genome 642
15.10 Protein-Tyrosine Phosphorylation as a The Role of p53 in Promoting Senescence 644
Mechanism for Signal Transduction 603
16.8 Other Tumor-Suppressor Genes 645
Receptor Dimerization 604
Protein Kinase Activation 604 16.9 Oncogenes 646
Phosphotyrosine-Dependent Protein–Protein Oncogenes That Encode Growth Factors or Their
Interactions 604 Receptors 646
Activation of Downstream Signaling Pathways 604 Oncogenes That Encode Cytoplasmic Protein Kinases 647
Ending the Response 607 Oncogenes That Encode Transcription Factors 647

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 Oncogenes That Encode Proteins That Affect the Epigenetic
18 Techniques in Cell and Molecular xix
State of Chromatin 647
Oncogenes That Encode Metabolic Enzymes 647 Biology 692

CONTENTS
Oncogenes That Encode Products
That Affect Apoptosis 648 18.1 The Light Microscope 693
Resolution 694
16.10 The Mutator Phenotype: Mutant Genes
Visibility 695
Involved in DNA Repair 649
18.2 Bright-Field and Phase-Contrast Microscopy 695
16.11 MicroRNAs: A New Player in the Genetics of
Cancer 649 Bright-Field Light Microscopy 695
Phase-Contrast Microscopy 695
16.12 The Cancer Genome 649
18.3 Fluorescence Microscopy (and Related
16.13 Gene-Expression Analysis 651 Fluorescence-Based Techniques) 696
16.14 Strategies for Combating Cancer 654 Laser Scanning Confocal Microscopy 699
16.15 Immunotherapy 654 Super-Resolution Fluorescence Microscopy 699
Light Sheet Fluorescence Microscopy 700
16.16 Inhibiting the Activity of Cancer-Promoting
Proteins 656 18.4 Transmission Electron Microscopy 701
16.17 The Concept of a Cancer Stem Cell 658 18.5 Specimen Preparation for Electron
16.18 Inhibiting the Formation of New Blood Vessels Microscopy 703
(Angiogenesis) 659 Cryofixation and the Use of Frozen Specimens 703
Negative Staining 705
Shadow Casting 705
17 The Immune Response 661 Freeze-Fracture Replication and Freeze Etching 705

17.1 An Overview of the Immune Response 662 18.6 Scanning Electron Microscopy 707
Innate Immune Responses 663 18.7 Atomic Force Microscopy 708
Adaptive Immune Responses 665
18.8 The Use of Radioisotopes 709
17.2 The Clonal Selection Theory as It Applies to B
Cells 666 18.9 Cell Culture 710
1 7 .3 T HE HUM AN P E R S P E CTIVE: 18.10 The Fractionation of a Cell’s Contents by
Autoimmune Diseases 668 Differential Centrifugation 711
17.4 Vaccination 671 18.11 Purification and Characterization of Proteins by
1 7 .5 E X P E R IM E N TAL PAT HWAY S: Liquid Column Chromatography 712
The Role of the Major Histocompatibility Complex in Antigen Ion-Exchange Chromatography 712
Presentation 672 Gel Filtration Chromatography 712
17.6 T Lymphocytes: Activation and Mechanism of Affinity Chromatography 713
Action 675 18.12 Determining Protein–Protein Interactions 714
17.7 The Modular Structure of Antibodies 678 18.13 Characterization of Proteins by Polyacrylamide
17.8 DNA Rearrangements That Produce Genes Gel Electrophoresis 715
Encoding B- and T-Cell Antigen Receptors 681 SDS–PAGE 716
17.9 Membrane-Bound Antigen Receptor Two-Dimensional Gel Electrophoresis 716
Complexes 683 18.14 Characterization of Proteins by
17.10 The Major Histocompatibility Complex 684 Spectrometry 716
17.11 Distinguishing Self from Nonself 686 18.15 Characterization of Proteins by Mass
17.12 Lymphocytes Are Activated by Cell-Surface Spectrometry 716
Signals 689 18.16 Determining the Structure of Proteins and
Activation of Helper T Cells by Professional APCs 689 Multisubunit Complexes 717
Activation of B Cells by TH Cells 689 18.17 Fractionation of Nucleic Acids 719
17.13 Signal Transduction Pathways in Lymphocyte Separation of DNAs by Gel Electrophoresis 719
Activation 689 Separation of Nucleic Acids by Ultracentrifugation 719

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 xx 18.18 Nucleic Acid Hybridization 721 Transgenic Animals 733
Transgenic Plants 734
18.19 Chemical Synthesis of DNA 722
18.25 Gene Editing and Silencing 734
18.20 Recombinant DNA Technology 723
CONTENTS

In Vitro Mutagenesis 735

Restriction Endonucleases 723
Knockout Mice 735
Formation of Recombinant DNAs 723
RNA Interference 736
DNA Cloning 724
Genome Editing Using Engineered
18.21 Enzymatic Amplification of DNA by PCR 726 Nucleases 737
Process of PCR 727 18.26 The Use of Antibodies 738
Applications of PCR 728

18.22 DNA Sequencing 728

18.23 DNA Libraries 730 Glossary G-1
Genomic Libraries 731
Additional Reading A-1
cDNA Libraries 731

18.24 DNA Transfer into Eukaryotic Cells and Index I-1

Mammalian Embryos 732

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 Nobel Prizes Awarded for Research
in Cell and Molecular Biology Since 1958

Year Recipient* Prize Area of Research Pages in Text

2015 Tomas Lindahl Chemistry Mechanisms of DNA repair 532
Paul Modrich
Aziz Sancar
2014 Eric Betzig Chemistry Development of super-resolved fluorescence microscopy 699–700
W. E. Moerner
Stefan Hell
2013 James E. Rothman M&P Discoveries of machinery regulating vesicle traffic 263, 279
Randy W. Schekman
Thomas C. Südhof
2012 John B. Gurdon M & P** Animal cloning, nuclear reprogramming 483
Shinya Yamanaka Cell reprogramming 20, 489
Brian K. Kobilka Chemistry G protein‐coupled receptors 588
Robert J. Lefkowitz
2011 Bruce A. Beutler M&P Innate immunity 664
Jules A. Hoffmann
Ralph M. Steinman Dendritic cells and Adaptive immunity 676
2009 Venkatraman Ramakrishnan Chemistry Ribosome structure and function 453
Thomas A. Steitz
Ada E. Yonath
Eliazbeth H. Blackburn M&P Telomeres and telomerase 475
Carol W. Greider
Jack W. Szostak
2008 Francoise Barré‐Sinoussi M&P Discovery of HIV 23
Luc Montagnier
Harald zur Hausen Role of HPV in cancer 631
Martin Chalfie Chemistry Discovery and development of GFP 260, 697
Osamu Shimomura
Roger Tsien
2007 Mario R. Capecchi M&P Development of techniques for knockout mice 735
Martin J. Evans
Oliver Smithies
2006 Andrew Z. Fire M&P RNA Interference 430
Craig C. Mello
Roger D. Kornberg Chemistry Transcription in eukaryotes 412, 465
2004 Richard Axel M&P Olfactory receptors 603
Linda B. Buck
Aaron Ciechanover Chemistry Ubiquitin and proteasomes 509
Avram Hershko
Irwin Rose
2003 Peter Agre Chemistry Structure of membrane channels 143, 144
Roderick MacKinnon
2002 Sydney Brenner M&P Introduction of C. elegans 16
John Sulston as a model organism
H. Robert Horvitz Apoptosis in C. elegans 622
John B. Fenn Chemistry Electrospray ionization in MS 717
Koichi Tanaka MALDI in MS 717
Kurt Wüthrich NMR analysis of proteins 55
2001 Leland H. Hartwell M&P Control of the cell cycle 547, 550
Tim Hunt
Paul Nurse

f01-Nobel Prizes Awarded.indd 21 11/21/2015 5:27:32 PM

 Year Recipient* Prize Area of Research Pages in Text
2000 Arvid Carlsson M&P Synaptic transmission and signal transduction 164
Paul Greengard 614
Eric Kandel
1999 Günter Blobel M&P Protein trafficking 268
1998 Robert Furchgott M&P NO as intercellular messenger 620
Louis Ignarro
Ferid Murad
1997 Jens C. Skou Chemistry Na+/K+‐ATPase 152
Paul Boyer Mechanism of ATP synthesis 189, 190
John Walker
Stanley B. Prusiner M&P Protein nature of prions 63
1996 Rolf M. Zinkernagel M&P Recognition of virus‐infected cells by the immune 672
system
Peter C. Doherty
1995 Edward B. Lewis M&P Genetic control of embryonic development 15
Christiane Nüsslein‐Volhard
Eric Wieschaus
1994 Alfred Gilman M&P Structure and function of GTP‐binding (G) proteins 593
Martin Rodbell
1993 Kary Mullis Chemistry Polymerase chain reaction (PCR) 726
Michael Smith Site‐directed mutagenesis (SDM) 735
Richard J. Roberts M&P Intervening sequences 420
Phillip A. Sharp
1992 Edmond Fischer M&P Alteration of enzyme activity by phosphorylation/ 109, 600
dephosphorylation
Edwin Krebs
1991 Erwin Neher M&P Measurement of ion flux by patch‐clamp recording 143
Bert Sakmann
1990 Joseph E. Murray M&P Organ and cell transplantation in human disease 684
E. Donnall Thomas
1989 J. Michael Bishop M&P Cellular genes capable of causing malignant 633
transformation
Harold Varmus
Thomas R. Cech Chemistry Ability of RNA to catalyze reactions 425, 450
Sidney Altman
1988 Johann Deisenhofer Chemistry Bacterial photosynthetic reaction center 207
Robert Huber
Hartmut Michel
1987 Susumu Tonegawa M&P DNA rearrangements responsible for antibody diversity 681
1986 Rita Levi‐Montalcini M&P Factors that affect nerve outgrowth 379
Stanley Cohen
1985 Michael S. Brown M&P Regulation of cholesterol metabolism and endocytosis 319
Joseph L. Goldstein
1984 Georges Köhler M&P Monoclonal antibodies 738, 739
Cesar Milstein
Niels K. Jerne Antibody formation 666
1983 Barbara McClintock M&P Mobile elements in the genome 391, 392, 394
1982 Aaron Klug Chemistry Structure of nucleic acid‐protein complexes 55
1980 Paul Berg Chemistry Recombinant DNA technology 692, 723
Walter Gilbert DNA sequencing technology 728
Frederick Sanger
Baruj Bennacerraf M&P Major histocompatibility complex 684
Jean Dausset
George D. Snell
1978 Werner Arber M&P Restriction endonuclease technology 723
Daniel Nathans
Hamilton O. Smith
Peter Mitchell Chemistry Chemiosmotic mechanism of oxidative phosphorylation 176
1976 D. Carleton Gajdusek M&P Prion‐based diseases 63
1975 David Baltimore M&P Reverse transcriptase and tumor virus activity 633

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