Molecular Biology. Structure and Dynamics of Genomes and Proteomes

Cover
Half Title
Title Page
Copyright Page
Dedication
Table of Contents
Preface
Acknowledgments
About the Authors
Chapter 1 To the Cell and Beyond: The Realm of Molecular Biology
	1.1 Introduction
	1.2 The vital role of microscopy in biology
		The light microscope led to the first revolution in biology
		Biochemistry led to the discovery of the importance of macromolecules in life’s structure and processes
		The electron microscope provided another order of resolution
	1.3 Fine structure of cells and viruses as revealed by microscopy
	1.4 Ultrahigh resolution: Biology at the molecular level
		Fluorescence techniques allow for one approach to ultraresolution
		Confocal fluorescence microscopy allows observation of the fluorescence emitted by a particular substance in a cell
		FIONA provides ultimate optical resolution by use of fluorescence
		FRET allows distance measurements at the molecular level
		Single-molecule cryo-electron microscopy is a powerful new technique
		The atomic force microscope feels molecular structure
		X-ray diffraction and nuclear magnetic resonance provide resolution to the atomic level
		Chemical imaging, the new powerful combination of imaging techniques
	1.5 Molecular genetics: Another face of molecular biology
	Key concepts
	Further reading
	Videos on the Internet
Chapter 2 From Classical Genetics to Molecular Genetics
	2.1 Introduction
	2.2 Classical genetics and the rules of trait inheritance
		Gregor Mendel developed the formal rules of genetics
		Mendel’s laws have extensions and exceptions
		Genes are arranged linearly on chromosomes and can be mapped
		The nature of genes and how they determine phenotypes was long a mystery
	2.3 The great breakthrough to molecular genetics
		Bacteria and bacteriophage exhibit genetic behavior and serve as model systems
		Transformation and transduction allow transfer of genetic information
		The Watson–Crick model of DNA structure provided the final key to molecular genetics
	2.4 Model organisms
	2.5 Whole genomes and evolution
		Evolutionary theory: From Darwin to the present day
		Human-driven evolution: The story of Vavilov
		The tree of life based on sequencing of thousands of species: Back to the two-domain tree of life
	Key concepts
	Further reading
	Videos on the Internet
Chapter 3 Proteins
	3.1 Introduction
		Proteins are macromolecules with enormous variety in size, structure, and function
		Proteins are essential for the structure and functioning of all organisms
	3.2 Protein structure
		Proteins are homogeneous polypeptides and amino acids are their building blocks
		Fred Sanger and the sequence of insulin
		In proteins, amino acids are covalently connected to form polypeptides
	3.3 Levels of structure in the polypeptide chain
		The primary structure of a protein is a unique sequence of amino acids
		A protein’s secondary structure involves regions of regular folding stabilized by hydrogen bonds
		Each protein has a unique three-dimensional tertiary structure
		The tertiary structure of most proteins is divided into distinguishable folded domains
		Algorithms are now used to identify and classify domains in proteins of known sequence
		Some domains or proteins are intrinsically disordered
		Quaternary structure involves associations between protein molecules to form aggregated structures
	3.4 How do proteins fold?
		Folding can be a problem
		Chaperones help or allow proteins to fold
	3.5 How are proteins destroyed?
		The proteasome is the general protein destruction system
	3.6 The proteome and protein interaction networks
		New technologies allow a census of an organism’s proteins and their interactions
	Key concepts
	Further reading
	Videos on the Internet
Chapter 4 Nucleic Acids
	4.1 Introduction
		Protein sequences are dictated by nucleic acids
	4.2 Chemical structure of nucleic acids
		DNA and RNA have similar but different chemical structures
		Nucleic acids (polynucleotides) are polymers of nucleotides
	4.3 Physical structures of DNA
		Discovery of the B-DNA structure was a breakthrough in molecular biology
		A number of alternative DNA structures exist
		Although the double helix is quite rigid, it can be bent by bound proteins
		DNA can also form folded tertiary structures
		Closed DNA circles can be twisted into supercoils
	4.4 Physical structures of RNA
		RNA can adopt a variety of complex structures but not the B-form helix
	4.5 One-way flow of genetic information
	4.6 Methods used to study nucleic acids
	Key concepts
	Further reading
	Videos on the Internet
Chapter 5 Recombinant DNA: Principles and Applications
	5.1 Introduction
		Cloning of DNA involves several fundamental steps
	5.2 Construction of recombinant DNA molecules
		Restriction endonucleases and ligases are essential tools in cloning
	5.3 Vectors for cloning
		Genes coding for selectable markers are inserted into vectors during their construction
		Bacterial plasmids were the first cloning vectors
		Recombinant bacteriophages can serve as bacterial vectors
		Cosmids and phagemids expand the repertoire of cloning vectors
	5.4 Artificial chromosomes as vectors
		Bacterial artificial chromosomes meet the need for cloning very large DNA fragments in bacteria
		Eukaryotic artificial chromosomes provide proper maintenance and expression of very large DNA fragments in eukaryotic cells
	5.5 Expression of recombinant genes
		Expression vectors allow regulated and efficient expression of cloned genes
		Shuttle vectors can replicate in more than one organism
	5.6 Introducing recombinant DNA into host cells
		Numerous host-specific techniques are used to introduce recombinant DNA molecules into living cells
	5.7 Polymerase chain reaction and site-directed mutagenesis
	5.8 Sequencing of entire genomes
		Genomic libraries contain the entire genome of an organism as a collection of recombinant DNA molecules
		There are two approaches for sequencing large genomes
	5.9 Manipulating the genetic content of eukaryotic organisms
		Making a transgenic mouse involves numerous steps
		To inactivate, replace, or otherwise modify a particular gene, the vector must be targeted for homologous recombination at that particular site
	5.10 Practical applications of recombinant DNA technologies
		Hundreds of pharmaceutical compounds are produced in recombinant bacteria
		Plant genetic engineering is a huge but controversial industry
		Gene therapy is a complex multistep process aiming to correct defective genes or gene functions that are responsible for disease
		Delivering a gene into sufficient cells within a specific tissue and ensuring its subsequent long-term expression is a challenge
		CRISPR, the new technology to change genomic DNA sequence at a predefined position
		Jurassic Park or de-extinction
		Cloning of whole animals by nuclear transfer
	Key concepts
	Further reading
	Videos on the Internet
Chapter 6 Protein–Nucleic Acid Interactions
	6.1 Introduction
	6.2 DNA–protein interactions
		DNA–protein binding occurs by many modes and mechanisms
		Site-specific binding is the most widely used mode
		Most recognition sites fall into a limited number of classes
		Most specific binding requires the insertion of protein into a DNA groove
		Some proteins cause DNA looping
		There are a few major protein motifs of DNA-binding domains
		Helix–turn–helix motif interacts with the major groove
		Zinc fingers also probe the major groove
		Leucine zippers are especially suited for dimeric sites
	6.3 RNA–protein interactions
	6.4 Studying protein–nucleic acid interactions
	Key concepts
	Further reading
	Videos on the Internet
Chapter 7 The Genetic Code, Genes, and Genomes
	7.1 Genes as nucleic acid repositories of genetic information
		Our understanding of the nature of genes is constantly evolving
		The central dogma states that information flows from DNA to protein
		It was necessary to separate cellular RNAs to seek the adaptors
		Messenger RNA, tRNA, and ribosomes constitute the protein factories of the cell
	7.2 Relating protein sequence to DNA sequence in the genetic code
		The first task was to define the nature of the code
	7.3 Surprises from the eukaryotic cell: Introns and splicing
		Eukaryotic genes usually contain interspersed noncoding sequences
	7.4 Genes from a new and broader perspective
		Protein-coding genes are complex
		Genome sequencing has revolutionized the gene concept
		Mutations, pseudogenes, and alternative splicing all contribute to gene diversity
	7.5 Comparing whole genomes and new perspectives on evolution
		Genome sequencing reveals puzzling features of genomes
		How are DNA sequence types and functions distributed in eukaryotes?
	Key concepts
	Further reading
	Videos on the Internet
Chapter 8 Physical Structure of the Genomic Material
	8.1 Introduction
	8.2 Chromosomes of viruses and bacteria
		Generally, viruses are packages for minimal genomes
		Bacterial chromosomes are organized structures in the cytoplasm
		DNA-bending proteins and DNA-bridging proteins help to pack bacterial DNA
	8.3 Eukaryotic chromatin
		Eukaryotic chromosomes are highly condensed DNA–protein complexes segregated into a nucleus
		The nucleosome is the basic repeating unit of eukaryotic chromatin
		Histone nonallelic variants and postsynthetic modifications create a heterogeneous population of nucleosomes
		The nucleosome family is dynamic
		Nucleosome assembly in vivo uses histone chaperones
	8.4 Higher-order chromatin structure
		Nucleosomes along the DNA form a chromatin fiber
		The chromatin fiber is folded, but its structure remains controversial
		The organization of chromosomes in the interphase nucleus is still obscure
	8.5 Mitotic chromosomes
		Chromosomes condense and separate in mitosis
		A number of proteins are needed to form and maintain mitotic chromosomes
		Centromeres and telomeres are chromosome regions with special functions
		There are a number of models of mitotic chromosome structure
	Key concepts
	Further reading
	Videos on the Internet
Chapter 9 Transcription in Bacteria
	9.1 Introduction
	9.2 Overview of transcription
		There are aspects of transcription common to all organisms
		Transcription requires the participation of many proteins
		Transcription is rapid but is often interrupted by pauses
		Transcription can be visualized by electron microscopy
	9.3 RNA polymerases and transcription catalysis
		RNA polymerases are a large family of enzymes that produce RNA transcripts of polynucleotide templates
	9.4 Mechanics of transcription in bacteria
		Initiation requires a multisubunit polymerase complex, termed the holoenzyme
		The initiation phase of bacterial transcription is frequently aborted
		Elongation in bacteria must overcome topological problems
		There are several mechanisms for transcription termination in bacteria
		Antisense transcription in bacteria is widespread and might have numerous functions
		Understanding transcription in bacteria is useful in clinical practice
	Key concepts
	Further reading
	Videos on the Internet
Chapter 10 Transcription in Eukaryotes
	10.1 Introduction
		Transcription in eukaryotes is a complex, highly regulated process
		Eukaryotic cells contain multiple RNA polymerases, each specific for distinct functional subsets of genes
	10.2 Transcription by RNA polymerase II
		The yeast Pol II structure provides insights into transcriptional mechanisms
		The structure of Pol II is more evolutionarily conserved than its sequence
		Nucleotide addition during transcription elongation is cyclic
		Transcription initiation depends on multisubunit protein complexes that assemble at core promoters
		An additional protein complex is needed to connect Pol II to regulatory proteins
		Termination of eukaryotic transcription is coupled to polyadenylation of the RNA transcript
	10.3 Transcription by RNA polymerase I
	10.4 Transcription by RNA polymerase III
		RNA polymerase III specializes in transcription of small genes
	10.5 Transcription in eukaryotes: Pervasive and spatially organized
		Most of the eukaryotic genome is transcribed
		Transcription in eukaryotes is not uniform within the nucleus
		Active and inactive genes are spatially separated in the nucleus
	10.6 Methods for studying eukaryotic transcription
		A battery of methods is available for the study of transcription
	Key concepts
	Further reading
	Videos on the Internet
Chapter 11 Regulation of Transcription in Bacteria
	11.1 Introduction
	11.2 General models for regulation of transcription
		Regulation can occur via differences in promoter strength or use of alternative σ factors
		Regulation through ligand binding to RNA polymerase is called stringent control
	11.3 Specific regulation of transcription
		Regulation of specific genes occurs through cis–trans interactions with transcription factors
		Transcription factors are activators and repressors whose own activity is regulated in a number of ways
		Several transcription factors can act synergistically or in opposition to activate or repress transcription
	11.4 Transcriptional regulation of operons is important to bacterial physiology
		The lac operon is controlled by a dissociable repressor and an activator
		Control of the trp operon involves both repression and attenuation
		The same protein can serve as an activator or a repressor: the ara operon
	11.5 Other modes of gene regulation in bacteria
		DNA supercoiling is involved in both global and local regulation of transcription
		DNA methylation can provide specific regulation
	11.6 Coordination of gene expression in bacteria
		Networks of transcription factors form the basis of coordinated gene expression
	Key concepts
	Further reading
	Videos on the Internet
Chapter 12 Regulation of Transcription in Eukaryotes
	12.1 Introduction
	12.2 Regulation of transcription initiation: Regulatory regions and transcription factors
		Core and proximal promoters are needed for basal and regulated transcription
		Enhancers, silencers, insulators, and locus control regions are all distal regulatory elements
		Some eukaryotic transcription factors are activators, others are repressors, and still others can be either, depending on context
		Regulation can use alternative components of the basal transcriptional machinery
		Mutations in gene regulatory regions and in transcriptional machinery components lead to human diseases
	12.3 Regulation of transcriptional elongation
		The polymerase may stall close to the promoter
		Transcription elongation rate can be regulated by elongation factors
	12.4 Transcription regulation and chromatin structure
		What happens to nucleosomes during transcription?
	12.5 Regulation of transcription by histone modifications and variants
		Modification of histones provides epigenetic control of transcription
		Gene expression is often regulated by histone post-translational modifications
		Readout of histone post-translational modification marks involves specialized protein molecules
		Post-translational histone marks distinguish transcriptionally active and inactive chromatin regions
		Some genes are specifically silenced by post-translational modification in some cell lines
		Polycomb protein complexes silence genes through H3K27 trimethylation and H2AK119 ubiquitylation
		Heterochromatin formation at telomeres in yeast silences genes through H4K16 deacetylation
		HP1-mediated gene repression in the majority of eukaryotic organisms involves H3K9 methylation
		Poly(ADP)ribosylation of proteins is involved in transcriptional regulation
		Histone variants H2A.Z, H3.3, and H2A.Bbd are present in active chromatin
		MacroH2A is a histone variant prevalent in inactive chromatin
		Problems caused by chromatin structure can be fixed by remodeling
		Endogenous metabolites can exert rheostat control of transcription
	12.6 DNA methylation
		DNA methylation patterns in genomic DNA may participate in regulation of transcription
		Carcinogenesis alters the pattern of CpG methylation
		DNA methylation changes during embryonic development
		DNA methylation is governed by complex enzymatic machinery
		There are proteins that read the DNA methylation mark
	12.7 Long noncoding RNAs in transcriptional regulation
		Noncoding RNAs play surprising roles in regulating transcription
		The sizes and genomic locations of noncoding transcripts are remarkably diverse
	12.8 Methods for measuring the activity of transcriptional regulatory elements
	Key concepts
	Further reading
	Videos on the Internet
Chapter 13 Transcription Regulation in the Human Genome
	13.1 Introduction
		Rapid full-genome sequencing allows deep analysis
	13.2 Basic concepts of ENCODE
		ENCODE depends on high-throughput, massively processive sequencing and sophisticated computer algorithms for analysis
		The ENCODE project integrates diverse data relevant to transcription in the human genome
	13.3 Regulatory DNA sequence elements
		Seven classes of regulatory DNA sequence elements make up the transcriptional landscape
	13.4 Specific findings concerning chromatin structure from ENCODE
		Millions of DNase I-hypersensitive sites mark regions of accessible chromatin
		DNase I signatures at promoters are asymmetric and stereotypic
		Nucleosome positioning at promoters and around TF-binding sites is highly heterogeneous
		The chromatin environment at regulatory elements and in gene bodies is also heterogeneous and asymmetric
	13.5 ENCODE insights into gene regulation
		Distal control elements are connected to promoters in a complex network
		Transcription factor binding defines the structure and function of regulatory regions
		Transcription factors interact in a huge network
		TF-binding sites and TF structure co-evolve
		DNA methylation patterns show a complex relationship with transcription
	13.6 ENCODE overview
		What have we learned from ENCODE, and where is it leading?
		Certain methods are essential to ENCODE project studies
	13.7 Beyond the ENCODE project
	Key concepts
	Further reading
	Videos on the Internet
Chapter 14 RNA Processing
	14.1 Introduction
		Most RNA molecules undergo post-transcriptional processing
		There are four general categories of processing
		Eukaryotic RNAs exhibit much more processing than bacterial RNAs
	14.2 Processing of tRNAs and rRNAs
		tRNA processing is similar in all organisms
		All three mature ribosomal RNA molecules are cleaved from a single long precursor RNA
	14.3 Processing of eukaryotic mRNA: End modifications
		Eukaryotic mRNA capping is co-transcriptional
		Polyadenylation at the 3′-end serves a number of functions
		Chemical modifications of eukaryotic RNAs and their roles
	14.4 Processing of eukaryotic mRNA: Splicing
		The splicing process is complex and requires great precision
		Splicing is carried out by spliceosomes
		Splicing can produce alternative mRNAs
		Tandem chimerism links exons from separate genes
		Trans-splicing combines exons residing in the two complementary DNA strands
	14.5 Regulation of splicing and alternative splicing
		Splice sites differ in strength
		Exon–intron architecture affects splice-site usage
		Cis–trans interactions may stimulate or inhibit splicing
		RNA secondary structure can regulate alternative splicing
		Sometimes alternative splicing regulation needs no auxiliary regulators
		The rate of transcription and chromatin structure may help regulate splicing
	14.6 Self-splicing: Introns and ribozymes
		A fraction of introns is excised by self-splicing RNA
		There are two classes of self-splicing introns
	14.7 Overview: The history of an mRNA molecule
		Proceeding from the primary transcript to a functioning mRNA requires a number of steps
		mRNA is exported from the nucleus to the cytoplasm through nuclear pore complexes
		RNA sequence can be edited by enzymatic modification even after transcription
	14.8 RNA quality control and degradation
		Bacteria, archaea, and eukaryotes all have mechanisms for RNA quality control
		Archaea and eukaryotes utilize specific pathways to deal with different RNA defects
	14.9 Biogenesis and functions of small silencing RNAs
		All ssRNAs are produced by processing from larger precursors
	Key concepts
	Further reading
	Videos on the Internet
Chapter 15 Translation: The Players
	15.1 Introduction
	15.2 A brief overview of translation
		Three participants are needed for translation to occur
	15.3 Transfer RNA
		tRNA molecules fold into four-arm cloverleaf structures
		tRNAs are aminoacylated by a set of specific enzymes, aminoacyl-tRNA synthetases
		Aminoacylation of tRNA is a two-step process
		Quality control or proofreading occurs during the aminoacylation reaction
		Insertion of noncanonical amino acids into polypeptide chains is guided by stop codons
	15.4 Messenger RNA
		The Shine–Dalgarno sequence in bacterial mRNAs aligns the message on the ribosome
		Eukaryotic mRNAs do not have Shine–Dalgarno sequences but more complex 5′- and 3′-untranslated regions
		Overall translation efficiency depends on a number of factors
	15.5 Ribosomes
		The ribosome is a two-subunit structure comprising rRNAs and numerous ribosomal proteins
		Functional ribosomes require both subunits, with specific complements of RNA and protein molecules
		The small subunit can accept mRNA but must join with the large subunit for peptide synthesis to occur
		Ribosome assembly has been studied both in vivo and in vitro
		The expanding “riboverse”
	Key concepts
	Further reading
	Videos on the Internet
Chapter 16 Translation: The Process
	16.1 Introduction
	16.2 An overview of translation: How fast and how accurate?
	16.3 Advanced methodology for the analysis of translation
		Cryo-EM allows visualization of discrete kinetic states of ribosomes
		X-ray crystallography provides the highest resolution
		Single-pair fluorescence resonance energy transfer allows dynamic studies at the single-particle level
	16.4 Initiation of translation
		Initiation of translation begins on a free small ribosomal subunit
		Cryo-EM provides details of initiation complexes
		Start site selection in eukaryotes is complex
	16.5 Translational elongation
		Decoding means matching the codon to the anticodon-carrying aminoacyl-tRNA
		Accommodation denotes a relaxation of distorted tRNA to allow peptide bond formation
		Peptide bond formation is accelerated by the ribosome
		The formation of hybrid states is an essential part of translocation
		Structural information on bacterial elongation factors provides insights into mechanisms
		There is an exit tunnel for the peptide chain in the ribosome
		Translation elongation in eukaryotes involves even more factors
		Ribosome stalling during translation elongation
	16.6 Termination of translation
		RF3 aids in removing RF1 andRF
		Ribosomes are recycled after termination
		Our views of translation continue to evolve
	Key concepts
	Further reading
	Videos on the Internet
Chapter 17 Regulation of Translation
	17.1 Introduction
	17.2 Regulation of translation by controlling ribosome number
		Ribosome numbers in bacteria are responsive to the environment
		Ribosome numbers in eukaryotes: Control and consequences of dysregulation
		Synthesis of ribosomal components in bacteria is coordinated
		Regulation of the synthesis of ribosomal components in eukaryotes involves chromatin structure
	17.3 Regulation of translation initiation
		Regulation of translation initiation is ubiquitous and remarkably varied
		Regulation may depend on protein factors binding to the 5′- or 3′-ends of mRNA
		Cap-dependent regulation is the major pathway for controlling initiation
		Initiation may utilize internal ribosome entry sites
		5′–3′-UTR interactions provide a novel mechanism that regulates initiation in eukaryotes
		Riboswitches are RNA sequence elements that regulate initiation in response to stimuli
		Repeat-associated non-AUG translation
		MicroRNAs can bind to mRNA, thereby regulating translation
	17.4 Regulation of the elongation process
	17.5 mRNA stability and decay in eukaryotes
		The two major pathways of decay for nonfaulty mRNA molecules start with mRNA deadenylation
		The 5′ → 3′ pathway is initiated by the activities of the decapping enzyme Dcp
		The 3′ → 5′ pathway uses the exosome, followed by a different decapping enzyme, DcpS
		There are additional pathways for mRNA degradation
		Unused mRNA is sequestered in P bodies and stress granules
		Cells have several mechanisms that destroy faulty mRNA molecules
		mRNA molecules that contain premature stop codons are degraded through nonsense-mediated decay or NMD
		No-go decay (NGD) functions when the ribosome stalls during elongation
		Non-stop decay or NSD functions when mRNA does not contain a stop codon
	17.6 Summary of translation regulation
	Key concepts
	Further reading
	Videos on the Internet
Chapter 18 Protein Processing and Modification
	18.1 Introduction
	18.2 Structure of biological membranes
		Biological membranes are protein-rich lipid bilayers
		Numerous proteins are associated with biomembranes
	18.3 Protein translocation through biological membranes
		Protein translocation can occur during or after translation
		Membrane translocation in bacteria and archaea primarily functions for secretion
		Membrane translocation in eukaryotes serves a multitude of functions
		Integral membrane proteins have special mechanisms for membrane insertion
		Vesicles transport proteins between compartments in eukaryotic cells
	18.4 Proteolytic protein processing: Cutting, splicing, and degradation
		Proteolytic cleavage is sometimes used to produce mature proteins from precursors
		Some proteases can catalyze protein splicing
		Controlled proteolysis is also used to destroy proteins no longer needed
	18.5 Post-translational chemical modifications of side chains
		Modification of side chains can affect protein structure and function
		Phosphorylation plays a major role in signaling
		Acetylation mainly modifies interactions
		Several classes of glycosylated proteins contain added sugar moieties
		Mechanisms of glycosylation depend on the type of modification
		Ubiquitylation adds single or multiple ubiquitin molecules to proteins through an enzymatic cascade
		Specificity of ubiquitin targeting is determined by a special class of enzymes
		The structure of protein-ubiquitin conjugates determines the biological role of the modification
		Polyubiquitin marks proteins for degradation by the proteasome
		Sumoylation adds single or multiple SUMO molecules to proteins
	18.6 Protein co-translational folding
	18.7 The genomic origin of proteins
	Key concepts
	Further reading
	Videos on the Internet
Chapter 19 DNA Replication in Bacteria
	19.1 Introduction
	19.2 Features of DNA replication shared by all organisms
		Replication on both strands creates a replication fork
		Mechanistically, synthesis of new DNA chains requires a template, a polymerase, and a primer
		DNA replication requires the simultaneous action of two DNA polymerases
		Other protein factors are obligatory at the replication fork
	19.3 DNA replication in bacteria
		Bacterial chromosome replication is bidirectional, from a single origin of replication
		DNA polymerase III catalyzes replication in bacteria
		Sliding clamp β, or processivity factor, is essential for processivity
		The clamp loader organizes the replisome
		The full complement of proteins in the replisome is organized in a complex and dynamic way
		DNA polymerase I is necessary for maturation of Okazaki fragments
	19.4 The process of bacterial replication
		The replisome is a dynamic structure during elongation
	19.5 Initiation and termination of bacterial replication
		Initiation involves both specific DNA sequence elements and numerous proteins
		Termination of replication also employs specific DNA sequences and protein factors that bind to them
	19.6 DNA replication and bacterial cell cycle
	19.7 Bacteriophage and plasmid replication
		Rolling-circle replication is an alternative mechanism
		Phage replication can involve both bidirectional and rolling-circle mechanisms
	Key concepts
	Further reading
	Videos on the Internet
Chapter 20 DNA Replication in Eukaryotes
	20.1 Introduction
	20.2 Replication initiation in eukaryotes
		Replication initiation in eukaryotes proceeds from multiple origins
		Eukaryotic origins of replication have diverse DNA and chromatin structure depending on the biological species
		There is a defined scenario for formation of initiation complexes
		Re-replication must be prevented
		Histone methylation regulates onset of replication licensing
	20.3 Replication elongation in eukaryotes
		Eukaryotic replisomes both resemble and significantly differ from those of bacteria
		Other components of the bacterial replisome have functional counterparts in eukaryotes
		Eukaryotic elongation has some special dynamic features
	20.4 Replication of chromatin
		Chromatin structure is dynamic during replication
		Histone chaperones may play multiple roles in replication
		Both old and newly synthesized histones are required in replication
		Epigenetic information in chromatin must also be replicated
	20.5 The DNA end-replication problem and its resolution
		Telomerase solves the end-replication problem
		Alternative lengthening of telomeres pathway is active in telomerase-deficient cells
	20.6 Mitochondrial DNA replication
		Are circular mitochondrial genomes myth or reality?
		Models of mitochondrial genome replication are contentious
	20.7 Replication in viruses that infect eukaryotes
		Retroviruses use reverse transcriptase to copy RNA into DNA
	Key concepts
	Further reading
	Videos on the Internet
Chapter 21 DNA Recombination
	21.1 Introduction
	21.2 Homologous recombination
		Homologous recombination plays a number of roles in bacteria
		Homologous recombination has multiple roles in mitotic cells
		Meiotic exchange is essential to eukaryotic evolution
	21.3 Homologous recombination in bacteria
		End resection requires the RecBCD complex
		Strand invasion and strand exchange both depend on RecA
		Much concerning homologous recombination is still not understood
		Holliday junctions are the essential intermediary structures in HR
	21.4 Homologous recombination in eukaryotes
		Proteins involved in eukaryotic recombination resemble their bacterial counterparts
		HR malfunction is connected with many human diseases
		Meiotic recombination allows exchange of genetic information between homologous chromosomes in meiosis
	21.5 Nonhomologous recombination
		Transposable elements or transposons are mobile DNA sequences that change positions in the genome
		Many transposons are transcribed but only a few have known functions
		There are several types of transposons
		DNA class II transposons can use either of two mechanisms to transpose themselves
		Retrotransposons, or class I transposons, require an RNA intermediate
	21.6 Site-specific recombination
		Bacteriophage λ integrates into the bacterial genome by site-specific recombination
		Immunoglobulin gene rearrangements also occur through site-specific recombination
	Key concepts
	Further reading
	Videos on the Internet
Chapter 22 DNA Repair
	22.1 Introduction
	22.2 Types of lesions in DNA
		Natural agents, from both within and outside a cell, can change the information content of DNA
	22.3 Pathways and mechanisms of DNA repair
		DNA lesions are countered by a number of mechanisms of repair
		Thymine dimers are directly repaired by DNA photolyase
		The enzyme O6-alkylguanine alkyltransferase is involved in the repair of alkylated bases
		Nucleotide excision repair is active on helix-distorting lesions
		The role of TFIIH in NER
		Base excision repair corrects damaged bases
		Mismatch repair corrects errors in base pairing
		Methyl-directed mismatch repair in bacteria uses methylation on adenines as a guide
		Mismatch repair pathways in eukaryotes may be directed by strand breaks during DNA replication
		Repair of double-strand breaks can be error-free or error-prone
		Homologous recombination repairs double-strand breaks faithfully
		Nonhomologous end-joining restores the continuity of the DNA double helix in an error-prone process
	22.4 Translesion synthesis
		Many repair pathways utilize RecQ helicases
	22.5 Chromatin as an active player in DNA repair
		Histone variants and their post-translational modifications are specifically involved in DNA repair
	22.6 Summary of DNA repair
	22.7 Overview: The role of DNA repair in life
	Key concepts
	Further reading
	Videos on the Internet
Glossary
Index