Fundamental Molecular Biology E-Book

Lizabeth A. Allison

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1974

Veröffentlichungsjahr: 2021

Beschreibung

Fundamental Molecular Biology

Discover a focused and up to date exploration of foundational and core concepts in molecular biology

The newly revised Third Edition of Fundamental Molecular Biology delivers a selective and precise treatment of essential topics in molecular biology perfect for allowing students to develop an accurate understanding of the applications of the field. The book applies the process of discovery-observations, questions, experimental designs, results, and conclusions-with an emphasis on the language of molecular biology. Readers will easily focus on the key ideas they need to succeed in any introductory molecular biology course.

Fundamental Molecular Biology provides students with the most up to date techniques and research used by molecular biologists today. Readers of the book will have the support and resources they need to develop a concrete understanding of core and foundational concepts of molecular biology, without being distracted by outdated or peripheral material.

Readers will also benefit from the inclusion of:

• A thorough introduction to and comparison of eukaryotic and prokaryotic organisms illustrating the variation of cellular processes across organisms
• Tool boxes exploring up to date experimental methods and techniques used by molecular biologists
• Focus boxes providing detailed treatment of topics that delve further into experimental strategies
• Disease boxes placing complex regulatory pathways in their relevant context and illustrating key principles of molecular biology

Perfect for instructors and professors of introductory molecular biology courses, Fundamental Molecular Biology will also earn a place in the libraries of anyone seeking to improve their understanding of molecular biology with an insightful and well-grounded treatment of the core principles of the subject.

Leseprobe

Table of Contents

Cover

Title Page

Copyright

ABOUT THE COMPANION WEBSITE

CHAPTER ONE: The Beginnings of Molecular Biology

1.1 Introduction

1.2 Insights into the nature of the hereditary material

1.3 A model for the structure of DNA: The DNA double helix

1.4 The central dogma of molecular biology

1.5 An evolutionary framework for heredity

BIBLIOGRAPHY

CHAPTER TWO: The Structure of DNA

2.1 Introduction

2.2 Primary structure: the components of nucleic acids

2.3 Secondary structure of DNA

2.4 Unusual DNA secondary structures

2.5 Tertiary structure of DNA

BIBLIOGRAPHY

CHAPTER THREE: The Versatility of RNA

3.1 Introduction

3.2 RNA is involved in a wide range of cellular processes

3.3 Structural motifs of RNA

3.4 The discovery of RNA catalysis

3.5 RNA‐based genomes

BIBLIOGRAPHY

CHAPTER FOUR: Protein Structure and Folding

4.1 Introduction

4.2 Primary structure: amino acids and the genetic code

4.3 The three‐dimensional structure of proteins

4.4 Protein function and regulation of activity

4.5 Protein folding and misfolding

BIBLIOGRAPHY

CHAPTER FIVE: Genome Organization and Evolution

5.1 Introduction

5.2 Genome organization varies in different organisms

5.3 Packaging of the eukaryotic genome

5.4 The majority of the eukaryotic genome is noncoding

5.5 Lateral gene transfer contributes to genome evolution

5.6 Prokaryotic and viral genome organization

BIBLIOGRAPHY

CHAPTER SIX: DNA Replication and Telomere Maintenance

6.1 Introduction

6.2 Early insights into the mode of bacterial DNA replication

6.3 DNA polymerases are the enzymes that catalyze DNA synthesis from 5′ to 3′

6.4 The bacterial replisome

6.5 The eukaryotic replisome

6.6 Alternative modes of circular DNA replication

6.7 Telomere maintenance: the role of telomerase in DNA replication, aging, and cancer

BIBLIOGRAPHY

CHAPTER SEVEN: DNA Repair Pathways

7.1 Introduction

7.2 Mutations and DNA damage

7.3 Lesion bypass

7.4 Direct reversal of DNA damage

7.5 Repair of single base changes and structural distortions by removal of DNA damage

7.6 Double‐strand break repair by removal of DNA damage

BIBLIOGRAPHY

CHAPTER EIGHT: Transcription in Bacteria

8.1 Introduction

8.2 Mechanism of transcription

8.3 Insights into gene regulation from the lactose (lac) operon

8.4 Mode of action of transcriptional regulators

8.5 Control of gene expression by RNA

8.6 Gene regulatory networks

BIBLIOGRAPHY

CHAPTER NINE: Transcription in Eukaryotes

9.1 Introduction

9.2 Overview of transcriptional regulation

9.3 Protein‐coding gene regulatory elements

9.4 The general transcription machinery and mechanism of transcription

9.5 The role of specific transcription factors in gene regulation

9.6 Transcriptional coactivators and corepressors

9.7 Transcription complex assembly: the enhanceosome model versus the “hit‐and‐run” model

9.8 Regulated nuclear import and export of transcription factors

BIBLIOGRAPHY

CHAPTER TEN: Epigenetic Mechanisms of Gene Regulation

10.1 Introduction

10.2 Epigenetic markers

10.3 Genomic imprinting

10.4 X chromosome inactivation

10.5 Epigenetic control of transposable elements

10.6 Epigenetics and nutritional legacy

10.7 Allelic exclusion

BIBLIOGRAPHY

CHAPTER ELEVEN: RNA Processing and Posttranscriptional Gene Regulation

11.1 Introduction

11.2 The discovery of split genes

11.3 Splicing occurs by a variety of mechanisms

11.4 Cotranscriptional processing of nuclear pre‐mRNA

11.5 Alternative splicing

11.6 RNA editing

11.7 Post‐transcriptional gene regulation by RNAi

11.8 RNA turnover in the nucleus and cytoplasm

BIBLIOGRAPHY

CHAPTER TWELVE: The Mechanism of Translation

12.1 Introduction

12.2 Ribosome structure and assembly

12.3 Aminoacyl‐tRNA synthetases

12.4 Initiation of translation

12.5 Elongation and events in the ribosome tunnel

12.6 Termination of translation

12.7 Translational and post‐translational control

BIBLIOGRAPHY

CHAPTER THIRTEEN: Recombinant DNA Technology and Genetically Modified Organisms

13.1 Introduction

13.2 The beginnings of recombinant DNA technology

13.3 Cutting and joining DNA

13.4 Molecular cloning

13.5 Library screening and probes

13.6 Restriction mapping and RFLP analysis

13.7 DNA sequencing

13.8 Introduction to genetically modified organisms

13.9 Transgenic mice: pronuclear microinjection

13.10 Gene targeting in mouse embryonic stem cells

13.11 CRISPR‐Cas gene editing

13.12 Applications of genetically modified animals

13.13 Cloning by nuclear transfer

13.14 Transgenic plants

BIBLIOGRAPHY

CHAPTER FOURTEEN: Tools for Analyzing Gene Organization, Expression, and Function

14.1 Introduction

14.2 DNA typing

14.3 Genomics, proteomics, and beyond

14.4 Whole‐genome sequencing

14.5 Reporter genes

14.6 Transcriptomics: RNA expression and localization

14.7 Proteomics: protein expression and localization

14.8 Analysis of nucleic acid–protein interactions

14.9 Analysis of protein–protein interactions

14.10 Structural analysis of proteins

BIBLIOGRAPHY

CHAPTER FIFTEEN: Medical Molecular Biology

15.1 Introduction

15.2 Genomic medicine

15.3 Molecular biology of cancer

15.4 Gene therapy

BIBLIOGRAPHY

APPENDIX

Chapter 1

Chapter 2

Chapter 3

Chapter 4

Chapter 5

Chapter 6

Chapter 7

Chapter 8

Chapter 9

Chapter 10

Chapter 11

Chapter 12

Chapter 13

Chapter 14

Chapter 15

GLOSSARY

Index

End User License Agreement

List of Tables

Chapter 2

Table 2.1 Nucleic acid nomenclature.

Table 2.2 Alternative forms of the DNA double helix.

a

.

Chapter 3

Table 3.1 RNPs are involved in a wide range of cellular processes.

Table 3.2 Types of naturally occurring ribozymes.

Table 3.3 Major types of RNA viruses that are human or veterinary pathogens.

Chapter 4

Table 4.1 The genetic code.

Table 4.2 The wobble hypothesis.

Table 4.3 Common and alternative meanings of codons.

Table 4.4 Some human protein misfolding diseases.

Chapter 5

Table 5.1 Cellular DNA content of various organisms or viruses.

Table 5.2 Diversity of DNA‐based genome organization.

Chapter 6

Table 6.1 The major players in DNA replication.

Table 6.2 The eukaryotic DNA polymerases.

a

Table 6.3 Telomerase activity.

Table 1 Symptoms of dyskeratosis congenita.

Chapter 7

Table 7.1 Types of nucleotide substitutions.

Table 7.2 DNA repair systems.

Table 1 Genes defective in xeroderma pigmentosum (XP).

Chapter 8

Table 8.1Alternative

E. coli

sigma (σ) factors.

Chapter 9

Table 9.1 Types of DNA‐dependent RNA polymerases.

Table 9.2 Some common eukaryotic promoter elements.

Table 9.3 Nuclear localization sequences and nuclear export sequences.

Chapter 10

Table 10.1 Monoallelic expression of mammalian genes.

Table 10.2 Genomic imprinting and neurodevelopmental disorders.

Table 10.3 Classes of transposable elements.

Chapter 12

Table 12.1 Components of ribosomes.

Table 12.2 Some comparisons between prokaryotic and eukaryotic translation.

Chapter 13

Table 13.1 Major classes of restriction endonucleases.

Table 13.2 rincipal features and applications of different cloning vector system...

Table 13.3 Some commonly used antibiotics and antibiotic resistance genes.

Table 1 Some radioisotopes commonly used in molecular biology research.

Table 1 Labeling of nucleic acids.

Table 13.4 omparison of transgenic technology, gene targeting, gene editing, and...

Table 13.5 History of cloning by nuclear transfer.

Chapter 14

Table 14.1 DNA polymorphisms used in forensic genetics.

Table 14.2Matching probabilities of 8 STR loci compared with 15 STR loci in vari...

Table 14.3 A selective sampling of sequenced eukaryotic genomes.

Table 14.4 Various cell transfection methods.

Table 14.5 A comparison of some commonly used reporter genes.

Table 14.6 Summary of some commonly used tools for analyzing gene expression.

Chapter 15

Table 15.1 Selective list of cancer predisposition syndromes.

Table 15.2 Selective list of viral oncogenes.

Table 15.3 Some chromosomal translocations associated with cancer.

Table 15.4 Gene therapy vectors.

List of Illustrations

Chapter 1

Figure 1.1 Three lines of research led to the discovery that DNA is the heredita...

Figure 1.2 Mendel's single‐trait (monohybrid) cross. The diagram s...

Figure 1.3 Incomplete dominance in snapdragon flower color. When a true‐bree...

Figure 1.4 Meiosis explains Mendel's law of segregation. The two members...

Figure 1.5 Meiosis explains Mendel's law of independent assortment. The ...

Figure 1.6 The transforming principle. Griffith's experiment with

Streptococ

...

Figure 1.7 The one gene–one enzyme hypothesis. The association between...

Figure 1.8 DNA is the genetic material of bacteriophage T2. The Hershey–Chas...

Figure 1.9 The DNA double helix. (a) James Watson (left) and Francis Crick a...

Figure 1.10 X‐ray diffraction photograph of DNA. (a) Rosalind Frankli...

Figure 1.11 The central dogma of molecular biology. Solid arrows show transf...

Figure 1.12 Evolution by natural selection. Different theories vary in how m...

Chapter 2

Figure 2.1 Components of nucleotides: sugars, bases, and phosphate. Primes a...

Figure 2.2 Chargaff's data showing the base composition of DNA.

Figure 2.3 Nucleoside and nucleotide structure. The structure of a nucleosid...

Figure 2.4 Formation of a nucleic acid chain. Nucleotides are linked by 5′ →...

Figure 2.5 The two common Watson–Crick base pairs of DNA. Adenine (A) ...

Figure 2.6 Non‐Watson–Crick base pairs. Hydrogen‐bond formation ...

Figure 2.7 Base stacking. (a) Two nucleotides in schematic form, showing the...

Figure 2.8 The DNA double helix has a hydrophobic core. (a) This picture sho...

Figure 2.9 Key features of the DNA double helix. The ribbon‐like strands rep...

Figure 2.10 The major groove carries a message that can be read by DNA‐bindi...

Figure 2.11 The structure of the B–Z junction. A region of Z‐DNA is co...

Figure 2.12 The denaturation, renaturation, and hybridization of double‐stra...

Figure 2.13 DNA denaturation curve. Double‐stranded DNA is heated, and its m...

Figure 2.14 Dependence of DNA denaturation on G + C content and on salt conc...

Figure 2.15 A DNA renaturation Cot curve. DNA is denatured to separate the t...

Figure 2.16 Comparison of Cot curves for Escherichia coli and calf thymus DN...

Figure 1 A DNA nanorobot for drug delivery. (a) Nanobot in a closed state. C...

Figure 2.17 Slipped structure and cruciform. (a) Slipped structure with comp...

Figure 2.18 Triple helix DNA and G‐quadruplex. (a) Triple helix DNA at...

Figure 2.19 Hoogsteen base pairs. (a) AT and (b) GC pairs. Hydrogen bonds ar...

Figure 2.20 DNA supercoiling. A linear DNA molecule of 10 complete turns (or...

Figure 2.21 Supercoiling occurs in nature. (a) The DNA of the bacteriophage ...

Chapter 3

Figure 3.1 Relationships among the eight major types of RNA during gene expr...

Figure 3.2 Components of RNA. The backbone of RNA is composed of alternating...

Figure 3.3 RNA secondary structure. Structural motifs in a typical secondary...

Figure 3.4 Base pairs found in RNA double helices. Hydrogen bonding (dotted ...

Figure 3.5 AGC and ACG base triples. The structures show two examples of hyd...

Figure 3.6 Secondary and tertiary structure of tRNA. (a) Upside‐down “clover...

Figure 3.7 Structure of modified bases found in tRNA. The structures of nucl...

Figure 3.8 RNA pseudoknot motif. (i) Conventional secondary structure of a p...

Figure 3.9 The A‐minor motif. (a) Example of an A‐minor motif from the...

Figure 3.10 Tetraloop motif. A stem loop with the tetraloop sequence UUUU is...

Figure 3.11 Ribose zipper motif. (a) The secondary structure of part of a la...

Figure 3.12 Kink‐turn motif. (a) Secondary structure of a kink‐turn mo...

Figure 3.13 Kissing hairpin loop motif. Two hairpin loops in RNA form a “kis...

Figure 3.14 Protein‐mediated RNA folding. The unfolded RNA molecule (t...

Figure 3.15 Hydroxyl radical footprinting of an RNA structure. A large RNA c...

Figure 3.16 Catalysts lower activation energies. The activation energy (E

A

) ...

Figure 1 The RNA world and the transition to the present DNA/RNA/protein wor...

Figure 3.17 Self‐splicing of Tetrahymena preribosomal RNA (pre‐rRNA)....

Figure 3.18 Maturation of tRNA catalyzed by RNase P. (a) The 5′ leader seque...

Figure 3.19 Similarity between self‐splicing RNA and protein‐based DNA polym...

Figure 3.20 Hammerhead ribozyme. The secondary structure of the hammerhead r...

Figure 1 Reassortment in influenza A virus. The influenza virus A genome is ...

Figure 2 The mosquito‐borne Zika virus can cause microcephaly in infants....

Figure 3.21 Examples of the diversity of eukaryotic RNA viruses. (a) Colored...

Chapter 4

Figure 4.1 The 22 genetically encoded amino acids found in proteins. At phys...

Figure 4.2 The acid–base properties of amino acids. The three major fo...

Figure 4.3 Peptide bond formation. Amino acids are joined by a condensation ...

Figure 4.4 Rigidity of the peptide bond. (a) The peptide bond acts as a part...

Figure 4.5 Translation of the genetic code. The diagram depicts the relation...

Figure 4.6 Decoding of a wobble base pair by the ribosome translation machin...

Figure 4.7

D

‐ and

L

‐configurations of aspartic acid (Asp).

Figure 4.8

D

‐Amino serine in spider venom. (a) An adult female America...

Figure 4.9 Four levels of protein structure. The primary protein structure i...

Figure 4.10 Disulfide bonds in tertiary folding. The backbone structure of α...

Figure 4.11 The structure of the globular protein lysozyme. (a) A ribbon mod...

Figure 4.12 Examples of the structures of some fibrous and transmembrane pro...

Figure 4.13 An example of the structure of a transmembrane protein. G protei...

Figure 4.14 Examples of protein quaternary structure. (a) Hemoglobin. Comput...

Figure 4.15 Structural comparison of levels of order and disorder in protein...

Figure 4.16 The photoactive yellow protein photoreceptor changes shape when ...

Figure 4.17 Tardigrade intrinsically disordered proteins (TDPs) protect them...

Figure 4.18 Enzymes such as lysozyme lower activation energies. The activati...

Figure 4.19 Lysozyme catalyzes the breakdown of polysaccharides from the Esc...

Figure 4.20 Levels of regulation of protein activity. Protein activity can b...

Figure 4.20 Levels of regulation of protein activity. Protein activity can b...

Figure 4.22 Allosteric regulation of enzyme activity. (a) Negative control. ...

Figure 4.23 Activation of cyclin‐dependent kinase (CDK) by cyclin binding an...

Figure 4.24 Regulation of protein folding. By associating with exposed hydrop...

Figure 4.25 Hsp90 chaperone function. Hsp90 mediates protein activation by u...

Figure 4.26 Ubiquitin–proteasome system. Ubiquitin (Ub) is attached to...

Figure 4.27 Chaperone‐mediated autophagy and macroautophagy. Misfolded...

Figure 4.28 Phase separation of macromolecules can form membraneless organel...

Figure 4.29 Amyloid‐like fibrils.(a) Light micrograph of a brain sectio...

Figure 1 Prions are infectious proteins. Prp

C

is synthesized, transported to...

Figure 2 Model for the propagation of prions.

Chapter 5

Figure 5.1 The three‐domain tree (a) and the two‐domain tree (b) for the div...

Figure 5.2 Genome size and organization versus the number of protein‐coding ...

Figure 5.3 The eukaryotic genome is located in the cell nucleus. A pancreati...

Figure 5.4 Male jumper jack ants have only one chromosome.

Figure 5.5 Micrococcal nuclease cleavage of chromatin reveals nucleosome rep...

Figure 5.6 Histones. Histone proteins isolated from chicken erythrocytes are...

Figure 5.7 A 10‐to‐11‐nm fiber showing the beads‐on‐a‐string structure....

Figure 5.8 Atomic structure of the core and linker histones. (a) A tetramer ...

Figure 5.9 Model of chromatin compaction. The DNA double helix (2 nm in dia...

Figure 5.10 Possible higher‐order nucleosome arrangements. (a) Chromat...

Figure 5.11 Lampbrush chromosomes. A medium‐sized lampbrush chromosome from ...

Figure 5.12 Condensin shapes chromosome structure. One model proposes that c...

Figure 5.13 Light micrograph of human chromosomes. The chromosomes are stain...

Figure 5.14 Ki‐67 prevents metaphase chromosomes from sticking together....

Figure 5.15 Mitosis. During mitosis, chromosomes condense, congregate at the...

Figure 5.16 Centromere structure. In the nematode

Caenorhabditis elegans

, ce...

Figure 5.17 CENP‐A and kinetochores. (a) The histone variant CENP‐A tr...

Figure 5.18 Three levels of gene expression. Eukaryotic gene expression is r...

Figure 5.19 Formation of heterochromatin by phase separation.

Figure 5.20 Polytene chromosomes. (a)

Drosophila

polytene chromosomes joined...

Figure 5.21 Organization of the human genome. The human genome consists of ...

Figure 5.22 Transposable elements. Transposable elements are DNA sequences ...

Figure 5.23 Satellite DNA. Separation of main band and satellite DNA from th...

Figure 5.24 A model for the origin of eukaryotic cells. Eukaryotes may have ...

Figure 5.25 Organelle DNA. (a) Two mitochondria of mouse (

Peromyscus

) heart ...

Figure 5.26 Intercompartmental DNA transfer. Overview of known types of inte...

Figure 5.27 The bacterial nucleoid. (a) Electron micrograph of a thin sectio...

Figure 5.28 Schematic representation of a bacterium containing plasmid DNA. ...

Figure 5.29 Structures of archaeal and eukaryotic histones. A comparison of ...

Figure 5.30 Spindle‐shaped archaeal viruses. Electron micrographs show...

Figure 5.31 Diversity among bacteriophages in terms of tail length and capsi...

Figure 5.32 Chromatin formation in simian virus 40 (SV40). (a) Electron micr...

Chapter 6

Figure 6.1 The Meselson and Stahl experiment to determine the mode of DNA re...

Figure 6.2 Bacterial DNA replication. (a) Autoradiograph of replicating

E. c

...

Figure 6.3 DNA synthesis occurs from 5 ′ to 3′.The template strand directs w...

Figure 6.4 Model of semidiscontinuous DNA replication. The figure shows a bi...

Figure 6.5 Bacterial DNA polymerase I is shaped roughly like a hand. On the ...

Figure 6.6 The bacterial replisome. The enzymes required for DNA replication...

Figure 6.7 Relaxation of supercoiled plasmid DNA by topoisomerase I. Lane ...

Figure 6.8 Mechanism of action of a type I topoisomerase. The enzyme forms...

Figure 6.9 Mechanism of action of DNA gyrase, a type II topoisomerase. Stars ...

Figure 6.10 Eukaryotic DNA replication occurs at multiple origins. (a) Diagra...

Figure 6.11 Mapping eukaryotic DNA replication origins by two‐dimensional ag...

Figure 6.12 Eukaryotic DNA replication occurs in replication factories from ...

Figure 6.13 Prereplication complex formation at origins of replication. Af...

Figure 6.14 ORC is a molecular machine that stimulates prereplication comple...

Figure 6.15 Replication licensing events lead to origin activation only on...

Figure 6.16 Duplex unwinding at replication forks and RNA priming of leadi...

Figure 6.17 Polymerase switching and strand elongation. The sliding clamp ...

Figure 6.18 The eukaryotic replisome. The lagging strand is shown positioned ...

Figure 6.19 Schematic representation of a DNA–RFC–PCNA complex. A...

Figure 6.20 Model of DNA polymerase proofreading function. (a) DNA polymerase...

Figure 6.21 Removal of RNA primers by the endonuclease activity of FEN‐1....

Figure 6.22 Fill‐in of gaps left by primer removal and joining of Okazaki ...

Figure 6.23 Enzymatic ligation of DNA involves three steps. (1) An enzyme–...

Figure 6.24 Human DNA ligase I encircles DNA during ligation. Three domain...

Figure 6.25 Amplification of phage φX174 by rolling circle replication...

Figure 6.26 Amplification of Xenopus oocyte ribosomal DNA (rDNA) by rolling ...

Figure 6.27 Models for mitochondrial DNA replication. (a) The strand displ...

Figure 6.28 DNA end replication problem. A replication fork moving from an...

Figure 6.29 Fluorescence in situ hybridization (FISH) analysis of individual...

Figure 6.30 Identification of telomerase activity in

Tetrahymena

. Cell‐free e...

Figure 6.31 Synthesis of telomeric DNA by human telomerase. The 3′ nucleoti...

Figure 6.32 The secondary structure of vertebrate telomerase RNA. The positio...

Figure 6.33 Recruitment of telomerase to telomeres. (a) Still images from mo...

Figure 6.34 Model for telomere length regulation. The shelterin complex prote...

Figure 6.35 Electron micrograph showing a t‐loop in chromatin from chicken e...

Figure 6.36 Telomerase activity increases the lifespan of human somatic cell...

Figure 6.37 Telomerase gene therapy. Reactivation of telomerase by introduci...

Chapter 7

Figure 7.1 A point mutation can be permanently incorporated by DNA replicati...

Figure 7.2 Examples of types of point mutations in protein‐coding sequences....

Figure 7.3 Trinucleotide repeat expansion by slippage during DNA replication...

Figure 7.4 Types of DNA damage. (a) Deamination of cytosine to uracil. (b) A...

Figure 7.5 Model for translesion DNA synthesis. (1) The replication machiner...

Figure 7.6 DNA repair by photoreactivation. (a) Ultraviolet radiation (purpl...

Figure 7.7 DNA repair by methyl group removal. Methyltransferase catalyzes t...

Figure 7.8 Model of DNA replication‐coupled DNA–protein cross‐link (DPC) rep...

Figure 7.9 Model for DNA damage recognition by 8‐oxoguanine DNA glycosylase ...

Figure 7.10 Base excision repair pathway in mammalian cells. The diagram sho...

Figure 7.11 Mismatch repair pathway in mammalian cells. The five major steps...

Figure 7.12 The molecular switch model for the MSH sliding clamp. During mis...

Figure 7.13 Reconstitution of human mismatch repair in an

in vitro

system. M...

Figure 1 A child with xeroderma pigmentosum. Note the abnormal dark pigmenta...

Figure 7.14 Mammalian nucleotide excision repair pathway. The diagram shows ...

Figure 7.15 A model for lesion recognition by Rad4/XPC. (a) The three distin...

Figure 7.16 Model for mammalian DNA double‐strand break repair by homologous...

Figure 7.17 Structure of the Holliday junction. (a) Electron micrograph of a...

Figure 7.18 Model for mammalian DNA double‐strand break repair by nonhomolog...

Chapter 8

Figure 8.1 Transcription and translation are coupled in bacteria. (a) Electr...

Figure 8.2 Bacterial promoters have two distinct consensus sequences. The −3...

Figure 8.3 Crystal structure of the Thermus thermophilus RNA polymerase core...

Figure 8.4 Structure of bacterial sigma factor and the RNA polymerase holoen...

Figure 8.5 The sigma factor stimulates tight binding of RNA polymerase to th...

Figure 8.6 RNA polymerase explores the entire nucleoid “searching” for gene ...

Figure 8.7 Conformational changes during the five steps of transcription ini...

Figure 8.8 Sigma factor triggers promoter melting by capturing two highly co...

Figure 8.9 Transcription elongation. A transcription bubble and the essentia...

Figure 1 Movement of RNA polymerase induces supercoiling. As the RNA polymer...

Figure 2 RNA polymerase is a molecular motor. (a) Observation system (not to...

Figure 8.10 RNA polymerase (RNAP) switches from the tight structural form to...

Figure 8.11 Transcription termination. Rho‐independent (a) and Rho‐dependent...

Figure 8.12 The Jacob–Monod operon model. The model predicted the exis...

Figure 8.13 Gilbert and Müller‐Hill's experiment demonstrating that the Lac ...

Figure 8.14

Lac

operon induction by lactose. (a) The components of the

lac

...

Figure 8.15 Structures of lactose, allolactose, and the lactose analog IPTG.

Figure 8.16 The structural genes of the lac operon are transcribed as a poly...

Figure 8.17

lac

operon repression by the Lac repressor and glucose. Transcr...

Figure 8.18 The CAP–DNA complex. (a) Model showing the helix‐turn‐heli...

Figure 8.19 Allosteric changes in the Lac repressor. A ribbon diagram of the...

Figure 8.20 Lac repressor–DNA recognition. The hinge region of the DNA...

Figure 8.21 The Lac repressor is a tethered dimer of dimers. Lac tetramer bo...

Figure 8.22 Regulation of the arabinose operon. (a) The domain structure is ...

Figure 8.23 Regulation of the E. coli

trp

operon. (a) Repression mediated b...

Figure 8.24 Mechanisms of riboswitch gene control. (a) Transcriptional atten...

Figure 8.25 A ribozyme riboswitch. (a) In the presence of GlcN6P, the GlmS r...

Figure 8.26 A sigma factor cascade. (a)

Scanning electron micrograph

(

SEM

) o...

Figure 8.27 Quorum sensing in bacteria. The LuxIR‐type quorum‐sensing system...

Chapter 9

Figure 9.1 Transcription and translation are uncoupled in eukaryotes. Transc...

Figure 9.2 Chromosome territories and transcription factories. (a) A human m...

Figure 1 Lamin A truncation in Hutchinson–Gilford progeria, a premature agin...

Figure 9.3 Comparison of a simple and complex RNA polymerase II transcriptio...

Figure 9.4 A TATA box–containing region promotes specific initiation of tran...

Figure 9.5 Characteristics of an enhancer element. An enhancer element can a...

Figure 9.6 Insulated neighborhoods. A CTCF‐bound DNA site interacts with ano...

Figure 9.7 Insulators function as chromatin boundary markers and have enhanc...

Figure 1 Hispanic thalassemia and DNase I sensitivity. (a) An approximately ...

Figure 9.8 Various views of the structure of RNA polymerase II. (a) Surface ...

Figure 9.9 Assembly of a stable preinitiation complex for RNA polymerase II ...

Figure 9.10 TBP bound to DNA. The saddle‐like structure of the TATA‐binding ...

Figure 9.11 The discovery of Mediator. (a) In this G‐less cassette assay, th...

Figure 9.12 Mediator: a molecular drawbridge. Mediator serves as a molecular...

Figure 9.13 Cryoelectron microscopy structure of the Mediator–preinitiation ...

Figure 9.14 Phase separation of Mediator and coactivators compartmentalizes a...

Figure 9.15 Initiation of transcription. (1) Promoter melting and pausing. A...

Figure 9.16 TFIIH helicase activity. DNA helicase activity unwinds the parti...

Figure 9.17 Transcription elongation. The general transcription elongation f...

Figure 9.18 Model of the tunable RNA polymerase II active site. (a) Proposed...

Figure 9.19 Transcription factors are composed of modular domains. The domai...

Figure 9.20 The helix‐turn‐helix DNA‐binding motif. (a) St...

Figure 1 Homeobox genes. (a) The

Hox

genes of

Drosophila

. Eight

Hox

genes re...

Figure 2 Model for how Polycomb group proteins silence developmental control...

Figure 9.21 The zinc finger DNA‐binding domain. (a) A schematic of the...

Figure 1 Greig cephalopolysyndactyly syndrome and Sonic hedgehog signaling. ...

Figure 9.22 Leucine zipper and basic helix‐loop‐helix motifs. (a...

Figure 9.23 Cooperative binding of Fos and Jun to DNA. A

32

P‐labeled DNA tha...

Figure 9.24 Post‐translational modification of histone N‐terminal tails....

Figure 1 Histone modifications are recognition landmarks for chromatin‐bindi...

Figure 9.25 Repression of the

MyoD

gene by the linker histone H1b. The Msx1 ...

Figure 9.26 Various modes of ATP‐dependent chromatin remodeling. Nucle...

Figure 9.27 Binding of SWR1 to the nucleosome induces multiple changes. (1) ...

Figure 9.28 The SWR1 complex mediates replacement of a core histone with a v...

Figure 9.29 The IFN‐β enhanceosome. A two‐step model for enhanceo...

Figure 9.30 Protein dynamics within the nucleus. (a) Fluorescence recovery a...

Figure 9.31 Mechanisms of transcription through the nucleosome by RNA polyme...

Figure 1 Familial dysautonomia ( FD ). Expression of wild‐type (WT) and m...

Figure 1 The nuclear pore complex (NPC). Field emission scanning electron mi...

Figure 9.32 Karyopherins have a snail‐like structure. Crystal structur...

Figure 9.33 Nuclear import cycle. An importin binds to its NLS‐bearing cargo...

Figure 9.34 Schematic illustrations of the nuclear pore complex (NPC) transl...

Figure 9.35 The Ran guanine nucleotide switch. When Ran switches between nuc...

Figure 9.36 Nuclear export cycle. Exportins bind to their cargo in the nucle...

Figure 9.37 Comparison of the cytoplasmic and nuclear forms of an exportin. ...

Figure 9.38 Signal‐mediated nuclear import of NF‐κB. The pa...

Figure 9.39 Signal‐mediated import of the glucocorticoid receptor (GR)....

Chapter 10

Figure 10.1 Ernest E. Just in his lab at Howard University in 1916.

Figure 10.2 Inheritance of methylation states. (a) Structure of the normal D...

Figure 10.3 The DNA methylation clock. In this “epigenetic clock” model, a s...

Figure 10.4 Induction of BNIP3 gene expression by treatment with 5‐azadeoxyc...

Figure 10.5 CpG islands are protected from deamination. (a) The restriction ...

Figure 1 Folic acid and related pathways for synthesis of S‐adenosylmethion...

Figure 1 Trinucleotide repeat expansion in fragile X syndrome. (a) Schematic...

Figure 1 DNA methylation testing for Prader–Willi syndrome (PWS) and Angelma...

Figure 2 Bisulfite‐PCR method for distinguishing normal cytosine from 5‐meth...

Figure 10.6 Genomic imprinting throughout development. Imprinted genes are s...

Figure 10.7 Regulation of imprinting. Schematic representation of regulatory...

Figure 10.8 X chromosome inactivation in marsupials and placental mammals. T...

Figure 10.9 Initiation of X chromosome inactivation. Random inactivation of ...

Figure 10.10

XIST

interacts with the lamin B receptor ( LBR ).This interaction ...

Figure 10.11 X inactivation profile of the human X chromosome. Gene expressi...

Figure 10.12 Transposable elements in plants. (a) Using maize kernel phenoty...

Figure 10.13 Classes of transposable elements. (a) DNA transposons, e.g.

Tc1

Figure 1

Alu

element insertion in patients with Apert syndrome. (a, b) Ampli...

Figure 10.14 DNA transposons move by a “cut‐and‐paste” mechanism....

Figure 10.15 Structure of a

Tc1

/

mariner

transposase .The functional regions ...

Figure 10.16 Retrotransposons move by a “copy‐and‐paste” mechanism....

Figure 10.17 Methylation of a DNA transposon leads to flower variegation in ...

Figure 10.18 Heterochromatic siRNAs silence transposable elements. Double‐st...

Figure 10.19 Maternal dietary methyl supplementation and coat color of offsp...

Figure 10.20 Homothallic life cycle of

Saccharomyces cerevisiae

. A haploid y...

Figure 10.21 Mating‐type loci on Saccharomyces cerevisiae chromosome 3....

Figure 1 Life cycle of the African trypanosome. Scanning electron micrograph...

Figure 2 Symptoms of trypanosomiasis. The characteristic cyclical waves of f...

Figure 10.22 Variant surface glycoprotein (VSG) transcriptional control and ...

Figure 10.23 Mechanisms of antigen switching in trypanosomes. Mechanisms of

Figure 10.24 Expression site body (ESB) of

Trypanosoma brucei

. (a) The ESB (...

Figure 10.25 Antibody‐mediated immunity. The steps involved in antibod...

Figure 1 A model for a transposon origin of the V(D)J system. (1) A schemati...

Figure 10.26 Structure of an immunoglobulin (antibody) molecule. The light c...

Figure 10.27 Overview of the process of V(D)J recombination. (a) The light‐c...

Figure 10.28 Mechanism for V(D)J recombination. Recombination signal sequenc...

Chapter 11

Figure 11.1 Intervening sequences in the ovalbumin gene. The split gene stru...

Figure 11.2 Conventional split genes comprise exons and introns. The DNA seq...

Figure 11.3 Group I intron splicing pathway. (a) Group I introns are removed...

Figure 11.4 Group II intron splicing pathway. (a) Group II intron splicing o...

Figure 11.5 Mobile group I and II introns. (a) Group I intron “homing.” (b) ...

Figure 11.6 Archaeal intron splicing pathway. The conserved secondary struct...

Figure 11.7 Splicing mechanisms of tRNA introns. The tRNA splicing pathway o...

Figure 11.8 RNA processing is coupled to transcription. (a) RNA processing f...

Figure 11.9 The carboxyl terminus of the RNA polymerase II CTD is necessary ...

Figure 11.10 7‐Methylguanosine cap structure. The cap is added in the ...

Figure 11.11 Modification of RNA by N 6 ‐methyladenosine (m 6 A) affects a v...

Figure 11.12 Model for transcription termination. Newly synthesized mRNA is ...

Figure 11.13 The polyadenylation complex. Cleavage and polyadenylation speci...

Figure 11.14 Splicing‐independent and splicing‐dependent polyadenylation....

Figure 11.15 Structure of the spliceosome. (a) At 20‐Å (2.0‐nm) resolution, ...

Figure 11.16 The structure of human U1 snRNP. The three‐dimensional model sh...

Figure 1 SMN‐mediated snRNP assembly and localization. (a) A model for...

Figure 11.17 U1 snRNP is the first snRNP to bind the pre‐mRNA. Graph d...

Figure 11.18 The nuclear pre‐mRNA splicing pathway. Intron removal req...

Figure 11.19 Two steps of transesterification take place during pre‐mRNA spl...

Figure 11.20 The central spliceosomal component Prp8. The pre‐mRNA splicing ...

Figure 11.21 A model of the regulation of splicing. The recruitment of splic...

Figure 11.22 The distribution of the SR protein in nuclear “speckles.”...

Figure 11.23 Patterns of alternative splicing. Exons are depicted as colored...

Figure 1 Extreme alternative splicing. Schematic representation of the

Dscam

Figure 11.24 Model for N 6‐methyladenosine (m6A)‐dependent regulation of exo...

Figure 11.25 Alternative splicing of CaMKIIδ during mammalian heart developm...

Figure 11.26 Two major types of

trans

‐splicing. (a) Discontinuous grou...

Figure 11.27 Extensive post‐transcriptional editing of the cytochrome oxidas...

Figure 11.28 RNA editing requires proteins and RNAs encoded by mitochondrial...

Figure 11.29 General mechanisms of insertion and deletion RNA editing. Pre‐m...

Figure 11.30 The two main classes of RNA editing enzymes in mammals. Adenosi...

Figure 1 RNA editing and AMPA receptor Ca

2+

permeability.(a) Editing results...

Figure 11.31 Apolipoprotein B (ApoB) editing occurs post‐transcriptionally w...

Figure 11.32 Mechanism of siRNA‐mediated RNA interference. The diagram...

Figure 11.33 RNAi in

Caenorhabditis elegans

. (a) Silencing of a GFP reporter...

Figure 11.34 siRNA‐guided mRNA cleavage by Argonaute. (a) Crystal stru...

Figure 11.35 The pathway of miRNA biogenesis. After the miRNA gene is transc...

Figure 11.36 Structural features of a typical miRNA hairpin. Structural feat...

Figure 11.37 Tissue‐specific gene expression for genes downregulated by miRN...

Figure 11.38 A model for pre‐mRNA quality control. Spliceosome assembl...

Figure 11.39 Alternate mRNA fates in the cytoplasm. Nuclear pre‐mRNA process...

Chapter 12

Figure 12.1 Electron micrographs of Escherichia coli small ribosomal subunit...

Figure 12.2 Classical three‐dimensional models of the E. coli ribosome....

Figure 12.3 Representation of the 70S E. coli ribosome from cryo‐EM studies....

Figure 12.4 Structure of the mammalian nucleolus. (a) Electron micrograph of...

Figure 12.5 Ribosomal RNA gene transcription.Schematic representation of h...

Figure 12.6 Ribosome biogenesis.Pathway for assembly in the nucleolus, mat...

Figure 12.7 The two steps of aminoacyl‐tRNA charging.The process is ...

Figure 12.8 Editing domain of ThrRS. (a) Comparison of the spatial arrangeme...

Figure 12.9 Translation initiation. An uncharged tRNA

Met

is first charged wi...

Figure 12.10 Models of cap‐dependent and cap‐independent initiation of trans...

Figure 1 Translation toeprint assay. (a) Principle of the translation assay....

Figure 12.11 Translation elongation in eukaryotes. An aminoacyl‐tRNA (in thi...

Figure 12.12 Incorporation of selenocysteine at a stop codon. Insertion of s...

Figure 12.13 Kinetics of tRNA selection on the ribosome. tRNA selection on t...

Figure 12.14 Peptidyltransferase region in the ribosome. The site of peptide...

Figure 12.15 In vitro “fragment reaction” to test for peptidyltransferase ac...

Figure 12.16 Sensitivity of Thermus aquaticus fragment reaction to peptidylt...

Figure 12.17 Atomic‐resolution structure of the ribosome. The large ri...

Figure 12.18 Secondary structure model of

E. coli

23S rRNA. The peptidyltran...

Figure 12.19 Cotranslation translocation pathway from the ribosome to the ...

Figure 12.20 Electron micrograph of rough endoplasmic reticulum (RER). RER i...

Figure 12.21 The

E. coli

trigger factor. Cryo‐EM structure of the trigger fa...

Figure 12.22 Termination of eukaryotic translation. The stop codons are reco...

Figure 12.23 Translational control by phosphorylation of eukaryotic initiati...

Figure 12.24 Model of the protein kinase RNA (PKR) activation pathway. PKR c...

Figure 12.25 Protein synthesis and eIF2α phosphorylation in reticulocytes fr...

Chapter 13

Figure 13.1 Bacteriophage lambda (λ) cohesive sites. In

Escherichia col

...

Figure 13.2 Restriction and modification systems in bacteria. Restriction en...

Figure 13.3 Cleavage patterns of some common restriction endonucleases. The ...

Figure 13.4 The steps involved in DNA binding and cleavage by a type II rest...

Figure 13.5 Modified blunt‐end ligation. Recombinant DNA molecules can...

Figure 13.6 Molecular cloning using a plasmid vector. A recombinant DNA mole...

Figure 1 Polymerase chain reaction (PCR). The target sequence to be amplifie...

Figure 13.7 Selection of recombinant clones by blue–white screening. R...

Figure 13.8 β‐Galactosidase activity can be used as an indicator of the pres...

Figure 1 Liquid chromatography techniques. (a) Gel filtration chromatography...

Figure 13.9 Use of bacteriophage lambda (λ) as a cloning vector. Each p...

Figure 13.10 Use of yeast artificial chromosome (YAC) cloning vectors. The Y...

Figure 1 Traditional cDNA synthesis. (a) Purification of mRNA. Total RNA is ...

Figure 1 Some methods for labeling nucleic acids. Two methods of uniform lab...

Figure 13.11 Screening a library by nucleic acid hybridization. The example ...

Figure 1 Agarose gel electrophoresis is used to separate DNA (and RNA) molec...

Figure 13.12 Analysis of recombinant DNA by restriction endonuclease digesti...

Figure 13.13 Diagnosis of sickle cell anemia by RFLP and Southern blot. Blac...

Figure 1 Southern blot. The steps involved in performing a Southern blot hyb...

Figure 1 Diagnosis of maple syrup urine disease (MSUD). (a) Degradation of t...

Figure 13.14 Sanger “dideoxy” DNA sequencing. (a) Four DNA synth...

Figure 13.15 Automated DNA sequencing. (a) The diagram depicts the steps inv...

Figure 13.16 Next‐generation Illumina sequencing. A library of single‐...

Figure 13.17 “Super” mouse. A transgenic mouse (left) expressing...

Figure 13.18 How to make a transgenic mouse. The three main stages in the st...

Figure 13.19 GFP‐expressingtransgenic mice. The photo in the left pane...

Figure 1 Sleeping Beauty transposase activates green fluorescent protein (GF...

Figure 13.20 Inducible transgene expression. The tetracycline (Tet)‐off syst...

Figure 13.21 How to make a knockout mouse. The five main stages involved in ...

Figure 13.22 Microinjection of a day 4 mouse blastocyst with embryo‐derived ...

Figure 13.23 Argonaute‐2 knockout mouse. The

Argonaute2

(

ago2

) gene wa...

Figure 13.24 Cre‐mediated recombination. The inverted repeats of the

l

...

Figure 13.25 Conditional gene knockout by Cre‐mediated recombination. ...

Figure 13.26 Adaptive immunity in bacteria. (a) The three stages of CRISPR‐C...

Figure 13.27 The four main steps of CRISPR‐Cas gene editing.

Figure 13.28 How to make a gene‐edited mouse. HDR, homology‐directed r...

Figure 13.29 AquaBounty's transgenic “AquAdvantage” salmon grows more quickl...

Figure 13.30 Example of a gene drive in mosquitoes. During early development...

Figure 13.31 Cloning of leopard frogs by nuclear transfer.

Figure 13.32 Clones of a South African clawed frog (

Xenopus laevis

). Clones ...

Figure 13.33 Dolly the cloned sheep. Dolly was cloned using the nucleus of a...

Figure 13.34 A photo gallery of clones. (a) Hooper the mouse shown with his ...

Figure 13.35 Cloning by nuclear transfer. Sheep are used as an example to il...

Figure 13.36 Primate nuclear transfer failures. (a) Defective mitotic spindl...

Figure 13.37 Model for why cloning by somatic cell nuclear transfer is ineff...

Figure 1 Genetically modified pets. (a) Glofish are transgenic zebrafish exp...

Figure 13.38 Cloning of endangered species. The example illustrates the impo...

Figure 13.39 Cloning for stem cells. The diagram shows a strategy for the th...

Figure 1 Transgenic tomatoes in supermarket.

Figure 13.40 How to make a transgenic plant. A common method for making tran...

Chapter 14

Figure 14.1 A billboard advertising paternity testing.

Figure 14.2 Simplified representation of minisatellite repeat analysis. For ...

Figure 14.3 Comparison of minisatellite repeat analysis using multilocus ver...

Figure 14.4 Multiplex short tandem repeat (STR) analysis. Electropherogram s...

Figure 14.5 Map of human mitochondrial DNA (mtDNA). Within the D loop, hyper...

Figure 14.6 Differentiation between Bacillus species by random amplification...

Figure 14.7 Example of a BLAST search. A sequence of amino acid residues fro...

Figure 14.8 Genome sequencing by the clone‐by‐clone approach. BA...

Figure 14.9 Shotgun sequencing.

Figure 1 Evolutionary relationship between humans, pufferfish, and other ver...

Figure 14.10 Gene prediction motif signals.

Figure 14.11 A transient transfection assay.

Figure 14.12 A stable transfection assay.

Figure 1 Antisense oligonucleotide–mediated inhibition of gene expression....

Figure 2 Structures of DNA and morpholino oligonucleotides. Morpholino oligo...

Figure 1

In vitro

mutagenesis. (a) Deletion mutagenesis by PCR. The cloned ...

Figure 14.13 A cotransfection assay. Reporter gene expression is activated b...

Figure 14.14 Commonly used purification and detection tags. (a) Histidine (H...

Figure 1 Comparison of the production of recombinant proteins in a bacterial...

Figure 1 Comparison of conventional fluorescence microscopy, confocal micros...

Figure 14.15 Properties of green fluorescent protein (GFP). (a) Formation of...

Figure 14.16 Use of green fluorescent protein (GFP) fusion proteins to visua...

Figure 14.17 Double labeling of HeLa cells with CFP‐tagged Golgi‐specific pr...

Figure 14.18 Comparison of methods for analysis of gene expression at the le...

Figure 14.19

In situ

hybridization. A labeled DNA or RNA probe is hybridized...

Figure 14.20 Reverse transcription–PCR (RT‐PCR).

Figure 14.21 Quantitative real‐time PCR. SYBR Green dye (green symbols...

Figure 14.22 DNA microarray. The method involves five main steps. (1) RNA is...

Figure 14.23 RNA sequencing (RNA‐seq).

Figure 1 One‐dimensional protein gel electrophoresis. (a) The method f...

Figure 2 Two‐dimensional protein gel electrophoresis. (a) The method f...

Figure 14.24 A Western blot. Note that although bands are shown on the gel a...

Figure 1 Polyclonal and monoclonal antibodies. (a) An antibody is composed o...

Figure 14.25 An indirect immunofluorescence assay. (Inset) Micrograph of cul...

Figure 14.26 Enzyme‐linked immunosorbent assay (ELISA). An example of ...

Figure 14.27 Protein arrays. (a) An analytical array. (b) A functional array...

Figure 14.28 Peptide mass fingerprinting using MALDI‐TOF. The process ...

Figure 14.29 Shotgun proteomics using tandem mass spectrometry (MS/MS). The ...

Figure 1 The nucleolar proteome. The steps in analysis of the proteome of th...

Figure 14.30 Electrophoretic mobility shift assay (EMSA).

Figure 14.31 Deoxyribonuclease I (DNase I) footprinting. (a) A diagram of ho...

Figure 14.32 Chromatin immunoprecipitation (ChIP) assay.

Figure 14.33 An

in vitro

GST pull‐down assay.

Figure 14.34

In vivo

analysis of protein–protein interactions. (a) Co...

Figure 14.35 Fluorescence resonance energy transfer (FRET). This method can ...

Figure 14.36 Solving protein structures. (a) X‐ray crystallography. Insets s...

Figure 14.37 Atomic force microscopy (AFM). (a) The diagram depicts an atomi...

Chapter 15

Figure 15.1 How disease genomics can lead to improvements in human health. ...

Figure 1 Single nucleotide polymorphism (SNP) in the apolipoprotein E gene i...

Figure 15.2 Two views of human behavior. (a) In an oversimplified model of h...

Figure 15.3 Functional polymorphism in the monoamine oxidase A (MAOA) gene i...

Figure 15.4 The progression of cancer. The growth of normal cells is restric...

Figure 15.5 Transformation of cells in culture. (a) A normal rat fibroblast ...

Figure 15.6 Inappropriate activation of proto‐oncogenes may be due to qualit...

Figure 15.7 Cellular localization and function of proto‐oncogene‐encodedprot...

Figure 15.8 Activation of c‐Src. (a) Comparison of the structure of hu...

Figure 15.9 Function of the c‐Myc transcription factor. The Myc–Max ba...

Figure 1 Knudson's two‐hit hypothesis and the development of retinoblastoma....

Figure 15.10 Retinoblastoma tumor suppressor protein (pRB): the cell cycle m...

Figure 15.11 Mechanisms of p53 degradation. p53 is maintained at low levels ...

Figure 15.12 Tumor suppressor protein p53: the “guardian of the genome.”...

Figure 15.13 Mutant p53 acts as a dominant negative protein in cancer. A mis...

Figure 1 Wild‐type p53 is a tumor suppressor protein. A p53 cDNA clone...

Figure 15.14 Oncogenic miRNA: overexpression of the mir‐17‐19b miRNA gene cl...

Figure 15.15 Chromosomal rearrangement in acute promyelocytic leukemia .A ch...

Figure 15.16

BCR

‐

ABL

rearrangement in chronic myelogenous leukemia. Th...

Figure 15.17 Treatment of chronic myelogenous leukemia. (a) Mechanism of act...

Figure 15.18 Possible outcomes of DNA tumor virus infection. (a) When a viru...

Figure 1 Human papillomavirus (HPV) and cancer. (a) Numerous flat warts on t...

Figure 15.19 Transformation of cells by retrovirus infection. The avian eryt...

Figure 15.20 Overview of genotoxic and nongenotoxic effects of carcinogens. ...

Figure 15.21 Tumor promotion through arylhydrocarbon receptor (AhR)‐mediated...

Figure 15.22 Two main strategies for somatic cell gene therapy. For

in vivo

...

Figure 15.23 Liposome‐mediated gene transfer. Complexes are formed bet...

Figure 1 Retroviral‐mediated gene transfer. The steps for preparation ...

Figure 15.24 “Schwarzenegger mice.” Transgenic mice were generat...

Figure 15.25 Insertional mutagenesis of the LMO2 proto‐oncogene in SCID‐X1 g...

Figure 15.26 The most common mutation in the

CFTR

gene. Approximately 70% of...

Figure 15.27 HIV‐1 infection. Colored transmission electron micrograph

Figure 1 Schematic of the seven major steps in the HIV‐1 life cycle. (...

Figure 15.28 Anti‐HIV‐1 LTRcatalytic antisense RNAs. Schematic r...

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Fundamental Molecular Biology

THIRD EDITION

Lizabeth A. Allison

College of William and MaryVirginiaUnited States

This third edition first published 2021

© 2021 John Wiley & Sons, Inc.

Edition History

© 2007 Lizabeth A. Allison; © 2012 John Wiley & Sons, Inc.

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Library of Congress Cataloging‐in‐Publication Data

Names: Allison, Lizabeth A., 1958‐ author.

Title: Fundamental molecular biology / Lizabeth A. Allison, College of

William and Mary Virginia, United States.

Description: Third edition. | Hoboken, NJ : Wiley‐Blackwell, 2021. |

Includes index.

Identifiers: LCCN 2020024332 (print) | LCCN 2020024333 (ebook) | ISBN

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Cover Image: © RM Floral/Alamy Stock Photo

ABOUT THE COMPANION WEBSITE

This book is accompanied by a companion website:

www.wiley.com/go/allison/FMB3

The website includes:

Powerpoints of figures.

CHAPTER ONEThe Beginnings of Molecular Biology

Science and everyday life cannot and should not be separated.

Rosalind Franklin in a letter to her father, Ellis Franklin, ca. summer 1940.

OUTLINE

1.1 Introduction

1.2 Insights into the nature of the hereditary material

1.3 A model for the structure of DNA: The DNA double helix

1.4 The central dogma of molecular biology

DNA in art.

(Susan Rankaitis, “DNA 2” from SPR Synthesis Project, 8′ × 16′, combined media, © 2002. Courtesy of Robert Mann Gallery.)

1.1 Introduction

What is molecular biology? In the broadest definition, molecular biology is the study of biological phenomena at the molecular level. Ask molecular biologists at a party what they do and they might narrow this definition to say that they study the molecular structure of DNA, the information it encodes, and the biochemical basis of gene expression and its regulation. For decades, such a declaration would have been a conversation stopper. DNA was largely an academic subject, not the source of dinner table conversation in the average household. In 1995 this changed when media coverage of the O.J. Simpson murder trial brought DNA fingerprinting to homes across the world. Two years later, the cloning of Dolly the sheep was headline news. Then, in 2001, scientists announced the rough draft of the human genome sequence. In commenting on this landmark achievement, former U.S. President Bill Clinton likened the “decoding of the book of life” to a medical version of the moon landing. More recently, CRISPR (clustered regularly interspaced short palindromic repeat)‐mediated genome editing has taken center stage. DNA now captivates Hollywood and the general public, excites scientists and science fiction writers, inspires artists, and challenges society with emerging ethical issues.

The last two decades mark the explosive growth of public awareness of molecular biology, but the real starting point of this field occurred when James D. Watson and Francis Crick suggested a structure for the salt of deoxyribonucleic acid(DNA). The history of the discovery of DNA – from its isolation as “nuclein” from soiled bandages, to proof that it is the universal hereditary material, to elucidation of the double helix structure in 1953 – is a riveting story (Figure 1.1). The details of this history are well beyond the scope of this text. Instead, this chapter presents some historical highlights that led to the beginnings of molecular biology. The selected examples set the scene for studying the many exciting discoveries that have occurred in more recent history – including within your own lifetime. This chapter also illustrates aspects of the process of science, how researchers test a hypothesis – a testable statement that explains a phenomenon or a set of observations – and how this process has led to fundamental theories. Note that in science the word “theory