Book Summary of Genes Vii
Oxford University Press is proud to present GENES VII--the latest edition of Benjamin Lewin's best-selling textbook. This authoritative work provides an integrated account of the structure and function of genes and incorporates all the latest research in the field.
THE MOST SIGNIFICANT REORGANIZATION TO DATE
The power of direct analysis of the genome has made a significant difference in the approach of GENES VII. In a departure from previous editions, which started with a traditional analysis of formal genetics, the new edition begins with the molecular properties of the gene itself. The text is now reorganized to begin with the concept of genes as a segment of DNA coding for protein, and then proceeds directly to the characterization of the genome in terms of its content of genes.
INTEGRATED APPROACH
GENES VII first explains the structure and function of the gene as a means to revealing the operation of the genome as a whole, and offers an integrated approach to prokaryotes and eukaryotes. The gene is considered from all aspects, including:
* Basic forms
* The numbers and relationships among genes in a genome
* Their packaging into chromosomes
* The process of gene expression from transcription through translation
* The reproduction and safeguarding of the gene structure
* Aspects of the overall circuitry through which genotype determines phenotype
STREAMLINED, FULL-COLOR DESIGN
GENES VII has been considerably restructured and reorganized to highlight the latest research and technology. It contains more than 800 full color illustrations that are extremely useful in teaching the key concepts presented in the book.
GENESVII CONTAINS NEW, GROUNDBREAKING INFORMATION ON:
* New technologies that count and compare expressed genes
* Accessory proteins (chaperones)
* The role of the proteasome
* Licensing
* Reverse translocation
* Connections between repair and recombination systems and human diseases
* Connections between the structure of chromosomal material and control of gene expression in eukaryotes
* The process of X chromosome inactivation
* Imprinting
* Control of gene expression by epigenetic changes
* The enzymatic activities that control chromatin structure and affect the regulatory process
* Archeael enzymes
* The mechanism of RNA editing in lower eukaryotes
* The role of RAG genes
* Interactions within and between pathways
* The use of protein degradation to control passage through the cell cycle
* Programmed cell death
* Telomerase and its role in carcinogenesis. And much more
THE MOST SIGNIFICANT REORGANIZATION TO DATE
The power of direct analysis of the genome has made a significant difference in the approach of GENES VII. In a departure from previous editions, which started with a traditional analysis of formal genetics, the new edition begins with the molecular properties of the gene itself. The text is now reorganized to begin with the concept of genes as a segment of DNA coding for protein, and then proceeds directly to the characterization of the genome in terms of its content of genes.
INTEGRATED APPROACH
GENES VII first explains the structure and function of the gene as a means to revealing the operation of the genome as a whole, and offers an integrated approach to prokaryotes and eukaryotes. The gene is considered from all aspects, including:
* Basic forms
* The numbers and relationships among genes in a genome
* Their packaging into chromosomes
* The process of gene expression from transcription through translation
* The reproduction and safeguarding of the gene structure
* Aspects of the overall circuitry through which genotype determines phenotype
STREAMLINED, FULL-COLOR DESIGN
GENES VII has been considerably restructured and reorganized to highlight the latest research and technology. It contains more than 800 full color illustrations that are extremely useful in teaching the key concepts presented in the book.
GENESVII CONTAINS NEW, GROUNDBREAKING INFORMATION ON:
* New technologies that count and compare expressed genes
* Accessory proteins (chaperones)
* The role of the proteasome
* Licensing
* Reverse translocation
* Connections between repair and recombination systems and human diseases
* Connections between the structure of chromosomal material and control of gene expression in eukaryotes
* The process of X chromosome inactivation
* Imprinting
* Control of gene expression by epigenetic changes
* The enzymatic activities that control chromatin structure and affect the regulatory process
* Archeael enzymes
* The mechanism of RNA editing in lower eukaryotes
* The role of RAG genes
* Interactions within and between pathways
* The use of protein degradation to control passage through the cell cycle
* Programmed cell death
* Telomerase and its role in carcinogenesis. And much more
Contents:
- Genes are DNA
- Introduction
- DNA is the genetic material
- DNA is a double helix
- DNA replication is semiconservative
- Nucleic acids hybridize by base pairing
- Mutations change the sequence of DNA
- Mutations are concentrated at hotspots
- A cistron is a single stretch of DNA
- The nature of multiple alleles
- Recombination occurs by physical exchange of DNA
- The genetic code is triplet
- The relationship between coding sequences and proteins
- cis-acting sites and trans-acting molecules
- Genetic information can be provided by DNA or RNA
- Summary
- From genes to genomes
- Introduction
- Genes can be mapped by restriction cleavage
- How variable are individual genomes?
- Eukaryotic genes are often interrupted
- Organization of interrupted genes may be conserved
- Exon sequences are conserved but introns vary
- Genes can be isolated by the conservation of exons
- Genes show a wide distribution of sizes
- Some DNA sequences code for more than one protein
- How did interrupted genes evolve?
- The scope of the paradigm
- Summary
- How many genes are there?
- Introduction
- Why are genomes so large?
- Total gene number is known for several organisms
- How many genes are essential?
- How many genes are expressed?
- Organelles have DNA
- Organelle genomes are circular DNAs that code for organelle proteins
- Mitochondrial DNA codes for few proteins
- The chloroplast genome codes for ~100 proteins and RNAs
- Summary
- Clusters and repeats
- Introduction
- Gene clusters are formed by duplication and divergence
- Sequence divergence is the basis for the evolutionary clock
- Pseudogenes are dead ends of evolution
- Unequal crossing-over rearranges gene clusters
- Genes for rRNA form tandem repeats
- The repeated genes for rRNA maintain constant sequence
- Crossover fixation could maintain identical repeats
- Satellite DNAs often lie in heterochromatin
- Arthropod satellites have very short identical repeats
- Mammalian satellites consist of hierarchical repeats
- Minisatellites are useful for genetic mapping
- Summary
- Messenger RNA
- Introduction
- Transfer RNA is the adapter
- Messenger RNA is translated by ribosomes
- The life cycle of messenger RNA
- Translation of eukaryotic mRNA
- The 5′ end of eukaryotic mRNA is capped
- The 3′ terminus is polyadenylated
- Bacterial mRNA degradation involves multiple enzymes
- Yeast mRNA degradation involves multiple activities
- Sequence elements may destabilize mRNA
- Nonsense mutations trigger a surveillance system
- Summary
- Protein synthesis
- Introduction
- The stages of protein synthesis
- Initiation in bacteria needs 30S subunits and accessory factors
- A special initiator tRNA starts the polypeptide chain
- Initiation involves base pairing between mRNA and rRNA
- Small subunits scan for initiation sites on eukaryotic mRNA
- Eukaryotes use a complex of many initiation factors
- Elongation factor T loads aminoacyl-tRNA into the A site
- Translocation moves the ribosome
- Three codons terminate protein synthesis
- Ribosomes have several active centers
- The organization of 16S rRNA
- 23S rRNA has peptidyl transferase activity
- Summary
- Using the genetic code
- Introduction
- Codon-anticodon recognition involves wobbling
- tRNA contains modified bases that influence its pairing properties
- There are sporadic alterations of the universal code
- tRNAs are charged with amino acids by synthetases
- Accuracy depends on proofreading
- Suppressor tRNAs have mutated anticodons that read new codons
- The accuracy of translation
- tRNA may influence the reading frame
- Summary
- Protein localization
- Introduction
- Chaperones may be required for protein folding
- The Hsp70 family is ubiquitous.
- Hsp60/GroEL forms an oligomeric ring structure
- Post-translational membrane insertion depends on leader sequences
- A hierarchy of sequences determines location within organelles
- Signal sequences initiate translocation
- The translocon forms a pore
- How do proteins enter and leave membranes?
- Anchor signals are needed for membrane residence
- Bacteria use both co-translational and post-translational translocation
- Pores are used for nuclear ingress and egress
- Nuclear pores are large symmetrical structures
- Proteins require signals to be transported through the pore
- Transport receptors carry cargo proteins through the pore
- Protein degradation by proteasomes
- Summary
- Transcription
- Introduction
- Transcription is catalyzed by RNA polymerase
- RNA polymerase consists of multiple subunits
- Sigma factor controls binding to DNA
- Promoter recognition depends on consensus sequences
- RNA polymerase binds to one face of DNA
- Substitution of sigma factors may control initiation
- Sigma factors may be organized into cascades
- Bacterial RNA polymerase has two modes of termination
- How does rho factor work?
- Antitermination depends on specific sites
- More subunits for RNA polymerase
- Summary
- The Operon
- Introduction
- Structural gene clusters are coordinately controlled
- Repressor is controlled by a small molecule inducer
- Mutations identify the operator and the regulator gene
- Repressor protein binds to the operator and is released by inducer
- The specificity of protein-DNA interactions
- Repression can occur at multiple loci
- Distinguishing positive and negative control
- Catabolite repression involves positive regulation at the promoter
- Adverse growth conditions provoke the stringent response
- Autogenous control may occur at translation
- Alternative secondary structures control attenuation
- Attenuation can be controlled by translation
- Small RNA molecules can regulate translation
- Summary
- Phage strategies
- Introduction
- Lytic development is controlled by a cascade
- Functional clustering in phages T7 and T4
- The lambda lytic cascade relies on antitermination
- Lysogeny is maintained by an autogenous circuit
- The DNA-binding form of repressor is a dimer
- Repressor binds cooperatively at each operator using a helix-turn-helix motif
- How is repressor synthesis established?
- A second repressor is needed for lytic infection
- A delicate balance: lysogeny versus lysis
- Summary
- The replicon
- Introduction
- Origins can be mapped by autoradiography and electrophoresis
- The bacterial genome is a single circular replicon
- Each eukaryotic chromosome contains many replicons
- Isolating the origins of yeast replicons
- D loops maintain mitochondrial origins
- The problem of linear replicons
- Rolling circles produce multimers of a replicon
- Single-stranded genomes are generated for bacterial conjugation
- Connecting bacterial replication to the cell cycle
- Cell division and chromosome segregation
- The division apparatus consists of cytoskeletal and regulatory components
- Partioning involves membrane attachment and (possibly) a motor
- Multiple systems ensure plasmid survival in bacterial populations
- Plasmid incompatibility is connected with copy number
- Summary
- DNA replication
- Introduction
- DNA polymerases are the enzymes that make DNA
- DNA polymerases have various nuclease activities
- DNA polymerases control the fidelity of replication
- Some DNA polymerases have a common structure
- DNA synthesis is semidiscontinuous
- Single-stranded DNA is needed for replication
- Priming is required to start DNA synthesis
- The primosome is needed to restart replication
- Coordinating synthesis of the lagging and leading strands
- The replication apparatus of phage T4
- Creating the replication forks at an origin
- Common events in priming replication at the origin
- Does methylation at the origin regulate initiation?
- Licensing factor controls eukaryotic rereplication
- Summary
- Recombination and repair
- Introduction
- Breakage and reunion involves heteroduplex DNA
- Double-strand breaks initiate recombination
- Double-strand breaks initiate synapsis
- The bacterial RecBCD system is stimulated by chi sequences
- RecA catalyzes single-strand assimilation
- The Ruv system resolves Holliday junctions
- Gene conversion accounts for interallelic recombination
- Topological manipulation of DNA
- Specialized recombination involves breakage and reunion at specific sites
- Repair systems correct damage to DNA
- Excision repair systems in E. coli
- Base flipping is used by methylases and glycosylases
- Error-prone repair and mutator phenotypes
- Controlling the direction of mismatch repair
- Retrieval systems in E. coli
- RecA triggers the SOS system
- Eukaryotic repair systems
- Summary
- Transposons
- Introduction
- Insertion sequences are simple transposition modules
- Composite transposons have IS modules
- Transposition occurs by both replicative and nonreplicative mechanisms
- Transposons cause rearrangement of DNA
- Common intermediates for transposition
- Replicative transposition proceeds through a cointegrate
- Nonreplicative transposition proceeds by breakage and reunion
- TnA transposition requires transposase and resolvase
- Transposition of Tn10 has multiple controls
- Controlling elements in maize cause breakage and rearrangements
- Controlling elements in maize form families of transposons
- Spm elements influence gene expression
- The role of transposable elements in hybrid dysgenesis
- Summary
- Retroviruses and retroposons
- Introduction
- The retrovirus life cycle involves transposition¡Vlike events
- Retroviruses may transduce cellular sequences
- Yeast Ty elements resemble retroviruses
- Many transposable elements reside in D. melanogaster
- Retroposons fall into two classes
- Summary
- Rearrangement of DNA
- Introduction
- The mating pathway is triggered by signal transduction
- Yeast can switch silent and active loci for mating type
- Silent cassettes at HML and HMR are repressed
- Unidirectional transposition is initiated by the recipient MAT locus
- Regulation of HO expression
- Trypanosomes rearrange DNA to express new surface antigens
- Interaction of Ti plasmid DNA with the plant genome
- Selection of amplified genomic sequences
- Exogenous sequences can be introduced into cells and animals by transfection
- Summary
- Chromosomes
- Introduction
- Condensing viral genomes into their coats
- The bacterial genome is a nucleoid with many supercoiled loops
- Loops, domains, and scaffolds in eukaryotic DNA
- The contrast between interphase chromatin and mitotic chromosomes
- The extended state of lampbrush chromosomes
- Transcription disrupts the structure of polytene chromosomes
- The eukaryotic chromosome as a segregation device
- Telomeres are simple repeats that seal the ends of chromosomes
- Telomeres are synthesized by a ribonucleoprotein enzyme
- Summary
- Nucleosomes
- Introduction
- The nucleosome is the subunit of all chromatin
- DNA is coiled in arrays of nucleosomes
- DNA structure varies on the nucleosomal surface
- Supercoiling and the periodicity of DNA
- The path of nucleosomes in the chromatin fiber
- Organization of the histone octamer
- Reproduction of chromatin requires assembly of nucleosomes
- Do nucleosomes lie at specific positions?
- Are transcribed genes organized in nucleosomes?
- DNAase hypersensitive sites change chromatin structure
- Domains define regions that contain active genes
- Heterochromatin depends on interactions with histones
- Global changes in X chromosomes
- Methylation is responsible for imprinting
- Epigenetic effects can be inherited
- Yeast prions show unusual inheritance
- Prions cause diseases in mammals
- Summary
- Initiation of transcription
- Introduction
- Eukaryotic RNA polymerases consist of many subunits
- Promoter elements are defined by mutations and footprinting
- RNA polymerase I has a bipartite promoter
- RNA polymerase III uses both downstream and upstream promoters
- The startpoint for RNA polymerase II
- TBP is a universal factor
- The basal apparatus assembles at the promoter
- A connection between transcription and repair
- Promoters for RNA polymerase II have short sequence elements
- Enhancers contain bidirectional elements that assist initiation
- Independent domains bind DNA and activate transcription
- Interaction of upstream factors with the basal apparatus
- Summary
- Regulation of transcription
- Introduction
- Response elements identify genes under common regulation
- There are many types of DNA-binding domains
- A zinc finger motif is a DNA-binding domain
- Steroid receptors have several independent domains
- Homeodomains bind related targets in DNA
- Helix-loop-helix proteins interact by combinatorial association
- Leucine zippers are involved in dimer formation
- Chromatin remodeling is an active process
- Histone acetylation and deacetylation control chromatin activity
- Polycomb and trithorax are antagonistic repressors and activators
- Long range regulation and insulation of domains
- Gene expression is associated with demethylation
- Summary
- Nuclear splicing and RNA processing
- Introduction
- Nuclear splice junctions are interchangeable but are read in pairs
- Nuclear splicing proceeds through a lariat
- The spliceosome contains snRNAs
- Group II introns autosplice via lariat formation
- Alternative splicing involves differential use of splice junctions
- cis-splicing and trans-splicing reactions
- Yeast tRNA splicing involves cutting and rejoining
- The 3′ ends of polI and polIII transcripts are generated by termination
- The 3′ ends of mRNAs are generated by cleavage
- Cleavage of the 3′ end may require a small RNA
- Production of rRNA requires cleavage and modification events
- Small RNAs are required for rRNA processing
- Summary
- Catalytic RNA
- Introduction
- Group I introns undertake self-splicing by transesterification
- Group I introns form a characteristic secondary structure
- Ribozymes have various catalytic activities
- Some introns code for proteins that sponsor mobility
- RNA can have ribonuclease activities
- RNA editing utilizes information from several sources
- Summary
- Immune diversity
- Introduction
- Clonal selection amplifies lymphocytes that respond to individual antigens
- Immunoglobulin genes are assembled from their parts in lymphocytes
- The diversity of germline information
- Recombination between V and C gene segments generates deletions and rearrangements
- Allelic exclusion is triggered by productive rearrangement
- DNA recombination causes class switching
- Somatic mutation generates additional diversity
- B cell development and memory
- T-cell receptors are related to immunoglobulins
- The major histocompatibility locus codes for many genes of the immune system
- Summary
- Protein trafficking
- Introduction
- Oligosaccharides are added to proteins in the ER and Golgi
- Coated vesicles transport both exported and imported proteins
- Different types of coated vesicles exist in each pathway
- An alternative model for protein transport
- Budding and fusion reactions
- Protein localization depends on further signals
- ER proteins are retrieved from the Golgi
- Receptors recycle via endocytosis
- Summary
- Signal transduction
- Introduction
- Carriers and channels form water soluble paths through the membrane
- G proteins may activate or inhibit target proteins
- Protein tyrosine kinases induce phosphorylation cascades
- The Ras/MAPK pathway
- Activating MAP kinase pathways
- Cyclic AMP and activation of CREB
- The JAK-STAT pathway
- TGFβ signals through Smads
- Structural subunits can be messengers
- Summary
- Cell cycle and growth regulation
- Introduction
- Cycle progression depends on discrete control points
- M phase kinase regulates entry into mitosis
- Protein phosphorylation and dephosphorylation control the cell cycle
- Cdc2 is the key regulator in yeasts
- CDC28 acts at both START and mitosis in S. cerevisiae
- The animal cell cycle is controlled by many cdk-cyclin complexes
- G0/G1 and G1/S transitions involve cdk inhibitors
- Protein degradation is important in mitosis
- Reorganization of the cell at mitosis
- Apoptosis is a property of many or all cells
- The Fas receptor is a major trigger for apoptosis
- A common pathway for apoptosis functions via caspases
- Apoptosis involves changes at the mitochondrial envelope
- There are multiple apoptotic pathways
- Summary
- Oncogenes and cancer
- Introduction
- Transforming viruses carry oncogenes
- Retroviral oncogenes have cellular counterparts
- Ras proto-oncogenes can be activated by mutation
- Insertion, translocation, or amplification may activate proto-oncogenes
- Oncogenes code for components of signal transduction cascades
- Growth factor receptor kinases and cytoplasmic tyrosine kinases
- Oncoproteins may regulate gene expression
- RB is a tumor suppressor that controls the cell cycle
- Tumor suppressor p53 suppresses growth or triggers apoptosis
- Immortalization and transformation
- Summary
- Gradients, cascades, and signaling pathways
- Introduction
- Fly development uses a cascade of transcription factors
- A gradient must be converted into discrete compartments
- Maternal gene products establish gradients in early embryogenesis
- Anterior development uses localized gene regulators
- Posterior development uses another localized regulator
- How are mRNAs and proteins transported and localized?
- Dorsal-ventral development uses localized receptor-ligand interactions
- TGFβ/BMPs are diffusible morphogens
- Cell fate is determined by compartments that form by the blastoderm stage
- The wingless/wnt signaling pathway
- Complex loci are extremely large and involved in regulation
- The homeobox is a common coding motif in homeotic genes
- Summary
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