基础分子生物学

出版时间：2008-6  出版社：高等教育出版社  作者：阿利森  页数：725  字数：950000  
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前言

　　The fast pace of modern molecular biology research is driven by intellectual curiosity and major challenges in medicine, agriculture, and industry. No discipline in biology has ever experienced the explosion in growth and popularity that molecular biology is now undergoing. There is intense public interest in the Human Genome Project and genetic engineering, due in part to fascination with how our own genes influence our lives. With this fast pace of discovery, it has been difficult to find a suitable, up-to-date textbook for a course in molecular biology. Other textbooks in the field flail into two categories: they are either too advanced, comprehensive, and overwhehmingly detailed, with enough material to fill an entire year or more of lectures, or they are too basic, superficial, and less experhmental in their approach. It is possible to piece together literature for a molecular biology course by assigning readings from a variety of sources. However, some students are poorly prepared to learn material strictly from lectures and selected readings in texts and the primary literature that do not match exactly the content of the course. At the other end, instructors may find it difficult to decide what topics are the most important to include in a course and what to exclude when presented with an extensive array of choices. This textbook aims to fill this perceived gap in the market. The intent is to keep the text to a manageable size while covering the essentials of molecular biology. Selection of topics to include or omit reflects my view of molecular biology and it is possible that some particular favorite topic may not be covered to the desired extent. Students often complain when an instructor teaches "straight from the textbook," so adding favorite examples is encouraged to allow instructors to enrich their course by bringing to it their own enthusiasm and insight.　　Approach　　A central theme of the textbook is the continuum of biological understanding, starting with basic properties of genes and genomes, RNA and protein structure and function, and extending to the complex, hierarchical interactions fundamental to living organisms. A comprehensive picture of the many ways molecular biology is being applied to the analysis of complex systems is developed, including advances that reveal fundamental features of gene regulation during cell growth and differentiation, and in response to a changing nvironment, as well as developments that are more related to commercial and medical applications. Recent advances in technology, the process and thrill of discovery, and ethical considerations in molecular biology research are emphasized.　 The text highlights the process of discovery - the observations, the questions, the experimental designs totest models, the results and conclusions - not just presenting the "facts." At the same time the language of molecular biology is emphasized, and a foundation is built that is based in fact. It is not feasible to examine every brick in the foundation and still have time to view the entire structure. However, as often as possible real examples of data are shown, e.g. actual results of an EMSA, Western blot, or RNA splicing assay. Experiments are selected either because they are classics in the field or because they illustrate a particular approach frequently used by molecular biologists to answer a diversity of questions.

内容概要

　　The beginnings of molecular biology , The structure of DNA
,Genome organization： from nucleotides to chromatin, The
versatility of RNA, From gene to protein, DNA replication and
telomere maintenance, DNA repair and recombination, Recombinant DNA
technology and molecular cloning。

书籍目录

1 The beginnings of molecular biology
1.1 Introduction
1.2 Historical perspective
Insights into heredity from round and wrinkled peas: Mendelian
genetics
Insights into the nature of hereditary materiaL: the transforming
principle is DNA
Creativity in approach leads to the one gene-one enzyme
hypothesis
The importance of technological advances: the Hershey-Chase
experiment
A model for the structure of DNA: the DNA double helix
Chapter summary
Analytical questions
Suggestions for further reading
2 The structure of DNA
2.1 Introduction
2.2 Primary structure: the components of nucleic acids
Five-carbon sugars
Nitrogenous bases
The phosphate functional group
Nucleosides and nucteotides
2.3 Significance of 5 and 3
2.4 Nomenclature of nucleotides
2.5 The length of RNA and DNA
2.6 Secondary structure of DNA
Hydrogen bonds form between the bases
Base stacking provides chemical stability to the DNA double
helix
Structure of the Watson-Crick DNA double helix
Distinguishing between features of alternative double-helical
structures
DNA can undergo reversible strand separation
2.7 Unusual DNA secondary structures
Slipped structures
Cruciform structures
Triple helix DNA
Disease box 2.1 Friedreichs ataxia and triple helix DNA
2.8 Tertiary structure of DNA
Supercoiling of DNA
Topoisomerases relax supercoiled DNA
What is the significance of supercoiting in vivo?
Disease box 2.2 Topoisomerase-targeted anticancer drugs
Chapter summary
Analytical questions
Suggestions for further reading
3 Genome organization: from nucleotides to chromatin
3.1 Introduction
3.2 Eukaryotic genome
Chromatin structure：historical perspective
Histones
Nucleosomes
Beads-on-a-string：the 10 nm fiber
The 30 nm fiber
Loop domains
Metaphase chromosomes
Alternative chromatin structures
3.3 Bacterial genome
3.4 Plasmids
3.5 Bacteriophages and mammalian DNA viruses
Bacteriophaqes
Mammalian DNA Viruses
3.6 Organelle genomes：chloroplasts and mitochondria
Chloroplast DNA(cpDNA)
Mitochondrial DNA (mtDNA)
Disease box 3.1 Mitochondrial DNA and disease
3.7 RNA-based genomes
Eukaryotic RNA viruses
Retroviruses
Viroids
Other Subviral pathoqens
Disease box 3.2 Avian flu
Chapter summary
Analytical questions
Suggestions for further reading
4 The versatility of RNA
4.1 Introduction
4.2 Secondary structure of RNA
Secondary structure motifs in RNA
Base-paired RNA adopts an A-type double helix
RNA helices often contain noncanonical base pairs
4.3 Tertiary structure of RNA
tRNA structure：important insiqhts into RNA structural motifs
Common tertiary structure motifs in RNA
4.4 Kinetics of RNA folding
4.5 RNA is involved in a wide range of cellular processes
4.6 Historical perspective：the discovery of RNA catalysis
Tetrahymena qroUP I intron ribozyme
RNase P ribozyme
Focus box 4.1：The RNA World
4.7 Ribozymes catalyze a variety of chemical reactions
Mode of ribozyme action
Large ribozymes
Small ribozymes
Chapter summary
Analytical questions
Suggestions for further reading
5 From gene to protein
5.1 Introduction
5.2 The central dogma
5.3 The genetic code
Translating the genetic code
The 21st and 22nd genetically encoded amino acids
Role of modified nucleotides in decoding
Implications of codon bias for molecular biologists
5.4 Protein structure
Primary structure
Secondary structure
Tertiary structure
Quaternary structure
Size and complexity of proteins
Proteins contain multiple functional domains
Prediction of protein structure
5.5 Protein function
Enzymes are biological catalysts
Regulation of protein activity by post-translational
modifications
Allosteric regulation of protein activity
Cyclin-dependent kinase activation
Macromolecular assemblages
5.6 Protein folding and misfolding
MoLecular chaperones
Ubiquitin-mediated protein degradation
Protein misfolding diseases
Disease box 5.1 Prions
Chapter summary
Analytical questions
Suggestions for further reading
6 DNA replication and telomere maintenance
6.1 Introduction
6.2 Historical perspective
Insight into the mode of DNA replication: the Meselson-Stahl
experiment
Insight into the mode of DNA replication: visualization of
replicating bacterial DNA
6.3 DNA synthesis occurs from 5→3
6.4 DNA polymerases are the enzymes that catalyze DNA
synthesis
Focus box 6.1 Bacterial DNA polymerases
6.5 Semidiscontinuous DNA replication
Leading strand synthesis is continuous
Lagging strand synthesis is discontinuous
6.6 Nuclear DNA replication in eukaryotic cells
Replication factories
Histone removal at the origins of replication
Prereplication complex formation at the origins of
replication
Replication Licensing: DNA only replicates once per cell
cycle
Duplex unwinding at replication forks
RNA priming of Leading strand and Lagging strand DNA
synthesis
Polymerase switching
Elongation of Leading strands and Lagging strands
Proofreading
Maturation of nascent DNA strands
Termination
Histone deposition
Focus box 6.2 The naming of genes involved in DNA replication
Disease box 6.1 Systemic lupus erythematosus and PCNA
6.7 Replication of organelle DNA
Models for mtDNA replication
Replication of cpDNA
Disease box 6.2 RNase MRP and cartilage-hair hypoplasia
6.8 Rolling circle replication
6.9 Tetomere maintenance: the role of tetomerase in DNA
replication, aging, and cancer
Telomeres
Solution to the end replication problem
Maintenance of telomeres by telomerase
Other modes of telomere maintenance
Regulation of telomerase activity
Telomerase, aging, and cancer
Disease box 6.3 Dyskeratosis congenita: loss of telomerase
function
Chapter summary
Analytical questions
Suggestions for further reading
7 DNA repair and recombination
7.1 Introduction
7.2 Types of mutations and their phenotypic consequences
Transitions and transversions can lead to silent, missense, or
nonsense mutations
Insertions or deletions can cause frameshift mutations
Expansion of trinucleotide repeats leads to genetic
instability
7.3 General classes of DNA damage
Single base changes
Structural distortion
DNA backbone damage
Cellular response to DNA damage
7.4 Lesion bypass
7.5 Direct reversal of DNA damage
7.6 Repair of single base changes and structural distortions by
removal of DNA damage
Base excision repair
Mismatch repair
Nucleotide excision repair
Disease box 7.1 Hereditary nonpolyposis colorectal cancer: a defect
in mismatch repair
7.7 Double-strand break repair by removal of DNA damage
Homologous recombination
Nonhomologous end-joining
Disease box 7.2 Xeroderma pigmentosum and related disorders:
defects in nucleotide excision repair
Disease box 7.3 Hereditary breast cancer syndromes: mutations in
BRCA1 and BRCA2
8 Recombinant DNA technology and molecular cloning
9 Tools for analyzing gene expression
10 Transcription in prokaryotes
11 Transcription in eukaryotes
12 Epigenetic and monoallelic gene expression
13 RNA processing and post-transcriptional gene regulation
14 The mechanism of translation
15 Genetically modified organisms: use in basic and applied
research
16 Genome analysis:DNA typing,genomics and beyond
17 Medical molecular biology
Glossary
Index

章节摘录

　　Other subviral pathogens　　Other subviral pathogens include satellite RNAs and virusoids. Viroids replicate autonomously by using host-encoded RNA polymerase. In contrast, satellite RNAs multiply only in the presence of a helper virus that provides the appropriate RNA-dependent RNA polymerase. Some of the larger satellite RNAs may encode a protein. Satellite RNAs are found in plants （e.g. satellite tobacco necrosis virus） and animals. A well known human satellite RNA is hepatitis delta virus （HDV）. HDV is a small single-stranded RNA satellite of hepatitis B virus.　　A virusoid is an RNA molecule that does not encode any proteins and depends on a helper virus for replication and capsid formation. Virusoids occur in association with viruses causing plant diseases such as velvet tobacco mottle and subterranean clover mottle. They are sometimes regarded as a subtype of satellite RNA. The virusoid genome resembles a viroid and consists of circular, single-stranded RNA with self-cleaving activity （see Section 4.7）.　　Chapter summary　　The genomes of most organisms are made of DNA; certain viruses and subviral pathogens have RNA genomes. Eukaryotic DNA combines with basic protein molecules called histones to form structures known as nucleosomes. Each nucleosome contains four pairs of core histones （H2A, H2B, H3, and H4） in a wedge-shaped disk, around which is wrapped 146 bp of DNA. The linker histone H1 is bound to DNA between the core histone octamers, where the DNA enters and exits the nucleosome. The first order of chromatin folding is represented by a string of nucleosomes. This 10 mn nucleosome fiber is further folded into a 30 nm fiber in a zig-zag ribbon structure, which is then folded into loop domains, and finally the metaphase chromosome. Each chromosome is composed of one linear, double-stranded DNA molecule.　　Bacterial chromosomal DNA exists as one double-stranded, circular DNA molecule organized into a condensed structure called a nucleoid. Plasmids are self-rephcating small, double-stranded, circular or linear DNA molecules carried by bacteria, some fungi, and some higher plants. Plasmids are important tools for recombinant DNA technology. Bacteriophages and mammalian DNA viruses have DNA genomes that occur in a variety of forms, ranging from double-stranded to single-stranded DNA and linear to circular forms. Viruses either package their genomes with their own basic proteins, or use host cell histones.　　Both mitochondria and chloroplasts contain their own genetic information. The small, double-stranded DNA genomes are usually, but not always, circular and there are multiple copies per organdie. Organelle genomes are maternally inherited.