LEWIN’S GENES XII · 2020. 4. 19. · Names: Krebs, Jocelyn E., author. | Goldstein, Elliott S., author. | Kilpatrick, Stephen T., author. Title: Lewin’s genes XII Other titles:

LEWIN’SGENESXIIJOCELYNE.KREBSUNIVERSITYOFALASKA,ANCHORAGE

ELLIOTTS.GOLDSTEINARIZONASTATEUNIVERSITY

STEPHENT.KILPATRICKUNIVERSITYOFPITTSBURGHATJOHNSTOWN

JONES&BARTLETT

LEARNING

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LibraryofCongressCataloging-in-PublicationDataNames:Krebs,JocelynE.,author.|Goldstein,ElliottS.,author.|Kilpatrick,StephenT.,author.Title:Lewin’sgenesXIIOthertitles:GenesXII|Lewin’sgenes12|Lewin’sgenestwelveDescription:Burlington,Massachusetts:Jones&BartlettLearning,[2018]|Includesindex.Identifiers:LCCN2016056017|ISBN9781284104493Subjects:|MESH:GeneticPhenomenaClassification:LCCQH430|NLMQU500|DDC576.5—dc23LCrecordavailableathttps://lccn.loc.gov/2016056017

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DEDICATIONToBenjaminLewin,forsettingthebarhigh.

Tomymother,EllenBaker,forraisingmewithaloveofscience;tothememoryofmystepfather,BarryKiefer,forconvincingmesciencewouldstayfun;tomywife,SusannahMorgan,fordecadesofloveandsupport;andtomyyoungsons,RhysandFrey,clearlybuddingyoungscientists(“Ihaveahypopesis”).Finally,tothememoryofmyPh.D.mentorDr.MariettaDunaway,agreatinspirationwhosetmyfeetontheexcitingpathofchromatinbiology.

—JocelynKrebs

Tomyfamily:mywife,Suzanne,whosepatience,understanding,andconfidenceinmeareamazing;mychildren,Andy,Hyla,andGary,whohavetaughtmesomuchaboutusingthecomputer;andmygrandchildren,SethandElena,whosesmilesandgigglesinspireme.Andtothememoryofmymentoranddearfriend,LeeA.Snyder,whoseprofessionalism,guidance,andinsightdemonstratedtheskillsnecessarytobeascientistandteacher.Ihavetriedtoliveuptohisexpectations.Thisisforyou,Doc.

—ElliottGoldstein

Tomyfamily:mywife,Lori,whoremindsmewhat’sreallyimportantinlife;mychildren,Jennifer,Andrew,andSarah,whofillmewithgreatprideandjoy;andmyparents,SandraandDavid,whoinspiredtheloveoflearninginme.

—StephenKilpatrick


BRIEFCONTENTS

PARTIGenesandChromosomes

Chapter1GenesAreDNAandEncodeRNAsandPolypeptidesEditedbyEstherSiegfried

Chapter2MethodsinMolecularBiologyandGeneticEngineering

Chapter3TheInterruptedGene

Chapter4TheContentoftheGenome

Chapter5GenomeSequencesandEvolution

Chapter6ClustersandRepeats

Chapter7ChromosomesEditedbyHankW.Bass

Chapter8ChromatinEditedbyCraigPeterson

PARTIIDNAReplicationandRecombination

Chapter9ReplicationIsConnectedtotheCellCycleEditedbyBarbaraFunnell

Chapter10TheReplicon:InitiationofReplication

Chapter11DNAReplication

Chapter12ExtrachromosomalReplicons

Chapter13HomologousandSite-SpecificRecombinationEditedbyHannahL.KleinandSamanthaHoot

Chapter14RepairSystems

Chapter15TransposableElementsandRetrovirusesEditedbyDamonLisch

Chapter16SomaticDNARecombinationandHypermutationintheImmuneSystemEditedbyPaoloCasali

PARTIIITranscriptionandPosttranscriptionalMechanisms

Chapter17ProkaryoticTranscription

Chapter18EukaryoticTranscription

Chapter19RNASplicingandProcessing

Chapter20mRNAStabilityandLocalizationEditedbyEllenBaker

Chapter21CatalyticRNAEditedbyDouglasJ.Briant

Chapter22Translation

Chapter23UsingtheGeneticCode

PARTIVGeneRegulation

Chapter24TheOperonEditedbyLiskinSwint-Kruse

Chapter25PhageStrategies

Chapter26EukaryoticTranscriptionRegulation

Chapter27EpigeneticsIEditedbyTrygveTollefsbol

Chapter28EpigeneticsIIEditedbyTrygveTollefsbol

Chapter29NoncodingRNA

Chapter30RegulatoryRNA


CONTENTSPrefaceAbouttheAuthors

PARTIGenesandChromosomes

Chapter1GenesAreDNAandEncodeRNAsandPolypeptidesEditedbyEstherSiegfried

1.1Introduction1.2DNAIstheGeneticMaterialofBacteriaandViruses1.3DNAIstheGeneticMaterialofEukaryoticCells1.4PolynucleotideChainsHaveNitrogenousBasesLinked

toaSugar—PhosphateBackbone1.5SupercoilingAffectstheStructureofDNA1.6DNAIsaDoubleHelix1.7DNAReplicationIsSemiconservative1.8PolymerasesActonSeparatedDNAStrandsatthe

ReplicationFork1.9GeneticInformationCanBeProvidedbyDNAorRNA1.10NucleicAcidsHybridizebyBasePairing1.11MutationsChangetheSequenceofDNA1.12MutationsCanAffectSingleBasePairsorLonger

Sequences1.13TheEffectsofMutationsCanBeReversed

1.14MutationsAreConcentratedatHotspots1.15ManyHotspotsResultfromModifiedBases1.16SomeHereditaryAgentsAreExtremelySmall1.17MostGenesEncodePolypeptides1.18MutationsintheSameGeneCannotComplement1.19MutationsMayCauseLossofFunctionorGainof

Function1.20ALocusCanHaveManyDifferentMutantAlleles1.21ALocusCanHaveMoreThanOneWild-TypeAllele1.22RecombinationOccursbyPhysicalExchangeofDNA1.23TheGeneticCodeIsTriplet1.24EveryCodingSequenceHasThreePossibleReading

Frames1.25BacterialGenesAreColinearwithTheirProducts1.26SeveralProcessesAreRequiredtoExpressthe

ProductofaGene1.27ProteinsAretrans-ActingbutSitesonDNAArecis-

Acting

Chapter2MethodsinMolecularBiologyandGeneticEngineering2.1Introduction2.2Nucleases2.3Cloning2.4CloningVectorsCanBeSpecializedforDifferent

Purposes2.5NucleicAcidDetection2.6DNASeparationTechniques2.7DNASequencing2.8PCRandRT-PCR

2.9BlottingMethods2.10DNAMicroarrays2.11ChromatinImmunoprecipitation2.12GeneKnockouts,Transgenics,andGenomeEditing

Chapter3TheInterruptedGene3.1Introduction3.2AnInterruptedGeneHasExonsandIntrons3.3ExonandIntronBaseCompositionsDiffer3.4OrganizationofInterruptedGenesCanBeConserved3.5ExonSequencesUnderNegativeSelectionAre

ConservedbutIntronsVary3.6ExonSequencesUnderPositiveSelectionVarybut

IntronsAreConserved3.7GenesShowaWideDistributionofSizesDuePrimarily

toIntronSizeandNumberVariation3.8SomeDNASequencesEncodeMoreThanOne

Polypeptide3.9SomeExonsCorrespondtoProteinFunctional

Domains3.10MembersofaGeneFamilyHaveaCommon

Organization3.11ThereAreManyFormsofInformationinDNA

Chapter4TheContentoftheGenome4.1Introduction4.2GenomeMappingRevealsThatIndividualGenomes

ShowExtensiveVariation4.3SNPsCanBeAssociatedwithGeneticDisorders4.4EukaryoticGenomesContainNonrepetitiveand

RepetitiveDNASequences

4.5EukaryoticProtein-CodingGenesCanBeIdentifiedbytheConservationofExonsandofGenomeOrganization

4.6SomeEukaryoticOrganellesHaveDNA4.7OrganelleGenomesAreCircularDNAsThatEncode

OrganelleProteins4.8TheChloroplastGenomeEncodesManyProteinsand

RNAs4.9MitochondriaandChloroplastsEvolvedby

Endosymbiosis

Chapter5GenomeSequencesandEvolution5.1Introduction5.2ProkaryoticGeneNumbersRangeOveranOrderof

Magnitude5.3TotalGeneNumberIsKnownforSeveralEukaryotes5.4HowManyDifferentTypesofGenesAreThere?5.5TheHumanGenomeHasFewerGenesThanOriginally

Expected5.6HowAreGenesandOtherSequencesDistributedin

theGenome?5.7TheYChromosomeHasSeveralMale-SpecificGenes5.8HowManyGenesAreEssential?5.9About10,000GenesAreExpressedatWidelyDiffering

LevelsinaEukaryoticCell5.10ExpressedGeneNumberCanBeMeasuredEnMasse5.11DNASequencesEvolvebyMutationandaSorting

Mechanism5.12SelectionCanBeDetectedbyMeasuringSequence

Variation

5.13AConstantRateofSequenceDivergenceIsaMolecularClock

5.14TheRateofNeutralSubstitutionCanBeMeasuredfromDivergenceofRepeatedSequences

5.15HowDidInterruptedGenesEvolve?5.16WhyAreSomeGenomesSoLarge?5.17MorphologicalComplexityEvolvesbyAddingNew

GeneFunctions5.18GeneDuplicationContributestoGenomeEvolution5.19GlobinClustersArisebyDuplicationandDivergence5.20PseudogenesHaveLostTheirOriginalFunctions5.21GenomeDuplicationHasPlayedaRoleinPlantand

VertebrateEvolution5.22WhatIstheRoleofTransposableElementsinGenome

Evolution5.23ThereCanBeBiasesinMutation,GeneConversion,

andCodonUsage

Chapter6ClustersandRepeats6.1Introduction6.2UnequalCrossing-OverRearrangesGeneClusters6.3GenesforrRNAFormTandemRepeatsIncludingan

InvariantTranscriptionUnit6.4CrossoverFixationCouldMaintainIdenticalRepeats6.5SatelliteDNAsOftenLieinHeterochromatin6.6ArthropodSatellitesHaveVeryShortIdenticalRepeats6.7MammalianSatellitesConsistofHierarchicalRepeats6.8MinisatellitesAreUsefulforDNAProfiling

Chapter7ChromosomesEditedbyHankW.Bass

7.1Introduction7.2ViralGenomesArePackagedintoTheirCoats7.3TheBacterialGenomeIsaNucleoidwithDynamic

StructuralProperties7.4TheBacterialGenomeIsSupercoiledandHasFour

Macrodomains7.5EukaryoticDNAHasLoopsandDomainsAttachedtoa

Scaffold7.6SpecificSequencesAttachDNAtoanInterphase

Matrix7.7ChromatinIsDividedintoEuchromatinand

Heterochromatin7.8ChromosomesHaveBandingPatterns7.9LampbrushChromosomesAreExtended7.10PolyteneChromosomesFormBands7.11PolyteneChromosomesExpandatSitesofGene

Expression7.12TheEukaryoticChromosomeIsaSegregationDevice7.13RegionalCentromeresContainaCentromericHistone

H3VariantandRepetitiveDNA7.14PointCentromeresinS.cerevisiaeContainShort,

EssentialDNASequences7.15TheS.cerevisiaeCentromereBindsaProteinComplex7.16TelomeresHaveSimpleRepeatingSequences7.17TelomeresSealtheChromosomeEndsandFunctionin

MeioticChromosomePairing7.18TelomeresAreSynthesizedbyaRibonucleoprotein

Enzyme7.19TelomeresAreEssentialforSurvival

Chapter8Chromatin

EditedbyCraigPeterson8.1Introduction8.2DNAIsOrganizedinArraysofNucleosomes8.3TheNucleosomeIstheSubunitofAllChromatin8.4NucleosomesAreCovalentlyModified8.5HistoneVariantsProduceAlternativeNucleosomes8.6DNAStructureVariesontheNucleosomalSurface8.7ThePathofNucleosomesintheChromatinFiber8.8ReplicationofChromatinRequiresAssemblyof

Nucleosomes8.9DoNucleosomesLieatSpecificPositions?8.10NucleosomesAreDisplacedandReassembledDuring

Transcription8.11DNaseSensitivityDetectsChangesinChromatin

Structure8.12AnLCRCanControlaDomain8.13InsulatorsDefineTranscriptionallyIndependent

Domains

PARTIIDNAReplicationandRecombination

Chapter9ReplicationIsConnectedtotheCellCycleEditedbyBarbaraFunnell

9.1Introduction9.2BacterialReplicationIsConnectedtotheCellCycle9.3TheShapeandSpatialOrganizationofaBacteriumAre

ImportantDuringChromosomeSegregationandCellDivision

9.4MutationsinDivisionorSegregationAffectCellShape9.5FtsZIsNecessaryforSeptumFormation

9.6minandnoc/slmGenesRegulatetheLocationoftheSeptum

9.7PartitionInvolvesSeparationoftheChromosomes9.8ChromosomalSegregationMightRequireSite-Specific

Recombination9.9TheEukaryoticGrowthFactorSignalTransduction

PathwayPromotesEntrytoSPhase9.10CheckpointControlforEntryintoSPhase:p53,a

GuardianoftheCheckpoint9.11CheckpointControlforEntryintoSPhase:Rb,a

GuardianoftheCheckpoint

Chapter10TheReplicon:InitiationofReplication10.1Introduction10.2AnOriginUsuallyInitiatesBidirectionalReplication10.3TheBacterialGenomeIs(Usually)aSingleCircular

Replicon10.4MethylationoftheBacterialOriginRegulatesInitiation10.5Initiation:CreatingtheReplicationForksattheOrigin

oriC10.6MultipleMechanismsExisttoPreventPremature

ReinitiationofReplication10.7ArchaealChromosomesCanContainMultiple

Replicons10.8EachEukaryoticChromosomeContainsMany

Replicons10.9ReplicationOriginsCanBeIsolatedinYeast10.10LicensingFactorControlsEukaryoticRereplication10.11LicensingFactorBindstoORC

Chapter11DNAReplication11.1Introduction

11.2DNAPolymerasesAretheEnzymesThatMakeDNA11.3DNAPolymerasesHaveVariousNucleaseActivities11.4DNAPolymerasesControltheFidelityofReplication11.5DNAPolymerasesHaveaCommonStructure11.6TheTwoNewDNAStrandsHaveDifferentModesof

Synthesis11.7ReplicationRequiresaHelicaseandaSingle-Stranded

BindingProtein11.8PrimingIsRequiredtoStartDNASynthesis11.9CoordinatingSynthesisoftheLaggingandLeading

Strands11.10DNAPolymeraseHoloenzymeConsistsof

Subcomplexes11.11TheClampControlsAssociationofCoreEnzymewith

DNA11.12OkazakiFragmentsAreLinkedbyLigase11.13SeparateEukaryoticDNAPolymerasesUndertake

InitiationandElongation11.14LesionBypassRequiresPolymeraseReplacement11.15TerminationofReplication

Chapter12ExtrachromosomalReplicons12.1Introduction12.2TheEndsofLinearDNAAreaProblemforReplication12.3TerminalProteinsEnableInitiationattheEndsofViral

DNAs12.4RollingCirclesProduceMultimersofaReplicon12.5RollingCirclesAreUsedtoReplicatePhageGenomes12.6TheFPlasmidIsTransferredbyConjugationBetween

Bacteria12.7ConjugationTransfersSingle-StrandedDNA

12.8Single-CopyPlasmidsHaveaPartitioningSystem12.9PlasmidIncompatibilityIsDeterminedbytheReplicon12.10TheColE1CompatibilitySystemIsControlledbyan

RNARegulator12.11HowDoMitochondriaReplicateandSegregate?12.12DLoopsMaintainMitochondrialOrigins12.13TheBacterialTiPlasmidCausesCrownGallDisease

inPlants12.14T-DNACarriesGenesRequiredforInfection12.15TransferofT-DNAResemblesBacterialConjugation

Chapter13HomologousandSite-SpecificRecombinationEditedbyHannahL.KleinandSamanthaHoot

13.1Introduction13.2HomologousRecombinationOccursBetween

SynapsedChromosomesinMeiosis13.3Double-StrandBreaksInitiateRecombination13.4GeneConversionAccountsforInterallelic

Recombination13.5TheSynthesis-DependentStrand-AnnealingModel13.6TheSingle-StrandAnnealingMechanismFunctionsat

SomeDouble-StrandBreaks13.7Break-InducedReplicationCanRepairDouble-Strand

Breaks13.8RecombiningMeioticChromosomesAreConnected

bytheSynaptonemalComplex13.9TheSynaptonemalComplexFormsAfterDouble-

StrandBreaks13.10PairingandSynaptonemalComplexFormationAre

Independent

13.11TheBacterialRecBCDSystemIsStimulatedbychiSequences

13.12Strand-TransferProteinsCatalyzeSingle-StrandAssimilation

13.13HollidayJunctionsMustBeResolved13.14EukaryoticGenesInvolvedinHomologous

Recombination1.EndProcessing/Presynapsis2.Synapsis3.DNAHeteroduplexExtensionandBranchMigration4.Resolution

13.15SpecializedRecombinationInvolvesSpecificSites13.16Site-SpecificRecombinationInvolvesBreakageand

Reunion13.17Site-SpecificRecombinationResembles

TopoisomeraseActivity13.18LambdaRecombinationOccursinanIntasome13.19YeastCanSwitchSilentandActiveMating-TypeLoci13.20UnidirectionalGeneConversionIsInitiatedbythe

RecipientMATLocus13.21AntigenicVariationinTrypanosomesUses

HomologousRecombination13.22RecombinationPathwaysAdaptedforExperimental

Systems

Chapter14RepairSystems14.1Introduction14.2RepairSystemsCorrectDamagetoDNA14.3ExcisionRepairSystemsinE.coli14.4EukaryoticNucleotideExcisionRepairPathways14.5BaseExcisionRepairSystemsRequireGlycosylases

14.6Error-ProneRepairandTranslesionSynthesis14.7ControllingtheDirectionofMismatchRepair14.8Recombination-RepairSystemsinE.coli14.9RecombinationIsanImportantMechanismtoRecover

fromReplicationErrors14.10Recombination-RepairofDouble-StrandBreaksin

Eukaryotes14.11NonhomologousEndJoiningAlsoRepairsDouble-

StrandBreaks14.12DNARepairinEukaryotesOccursintheContextof

Chromatin14.13RecATriggerstheSOSSystem

Chapter15TransposableElementsandRetrovirusesEditedbyDamonLisch

15.1Introduction15.2InsertionSequencesAreSimpleTransposition

Modules15.3TranspositionOccursbyBothReplicativeand

NonreplicativeMechanisms15.4TransposonsCauseRearrangementofDNA15.5ReplicativeTranspositionProceedsThrougha

Cointegrate15.6NonreplicativeTranspositionProceedsbyBreakage

andReunion15.7TransposonsFormSuperfamiliesandFamilies15.8TheRoleofTransposableElementsinHybrid

Dysgenesis15.9PElementsAreActivatedintheGermline

15.10TheRetrovirusLifeCycleInvolvesTransposition-LikeEvents

15.11RetroviralGenesCodeforPolyproteins15.12ViralDNAIsGeneratedbyReverseTranscription15.13ViralDNAIntegratesintotheChromosome15.14RetrovirusesMayTransduceCellularSequences15.15RetroelementsFallintoThreeClasses15.16YeastTyElementsResembleRetroviruses15.17TheAluFamilyHasManyWidelyDispersedMembers15.18LINEsUseanEndonucleasetoGenerateaPriming

End

Chapter16SomaticDNARecombinationandHypermutationintheImmuneSystemEditedbyPaoloCasali

16.1TheImmuneSystem:InnateandAdaptiveImmunity16.2TheInnateResponseUtilizesConservedRecognition

MoleculesandSignalingPathways16.3AdaptiveImmunity16.4ClonalSelectionAmplifiesLymphocytesThat

RespondtoaGivenAntigen16.5IgGenesAreAssembledfromDiscreteDNASegments

inBLymphocytes16.6LChainsAreAssembledbyaSingleRecombination

Event16.7HChainsAreAssembledbyTwoSequential

RecombinationEvents16.8RecombinationGeneratesExtensiveDiversity16.9V(D)JDNARecombinationReliesonRSSandOccurs

byDeletionorInversion

16.10AllelicExclusionIsTriggeredbyProductiveRearrangements

16.11RAG1/RAG2CatalyzeBreakageandReligationofV(D)JGeneSegments

16.12BCellDevelopmentintheBoneMarrow:FromCommonLymphoidProgenitortoMatureBCell

16.13ClassSwitchDNARecombination16.14CSRInvolvesAIDandElementsoftheNHEJPathway16.15SomaticHypermutationGeneratesAdditional

DiversityandProvidestheSubstrateforHigher-AffinitySubmutants

16.16SHMIsMediatedbyAID,Ung,ElementsoftheMismatchDNARepairMachinery,andTranslesionDNASynthesisPolymerases

16.17IgsExpressedinAviansAreAssembledfromPseudogenes

16.18ChromatinArchitectureDynamicsoftheIgHLocusinV(D)JRecombination,CSR,andSHM

16.19EpigeneticsofV(D)JRecombination,CSR,andSHM16.20BCellDifferentiationResultsinMaturationofthe

AntibodyResponseandGenerationofLong-livedPlasmaCellsandMemoryBCells

16.21TheTCellReceptorAntigenIsRelatedtotheBCR16.22TheTCRFunctionsinConjunctionwiththeMHC16.23TheMHCLocusComprisesaCohortofGenes

InvolvedinImmuneRecognition

PARTIIITranscriptionandPosttranscriptionalMechanisms

Chapter17ProkaryoticTranscription

17.1Introduction17.2TranscriptionOccursbyBasePairingina“Bubble”

ofUnpairedDNA17.3TheTranscriptionReactionHasThreeStages17.4BacterialRNAPolymeraseConsistsofMultiple

Subunits17.5RNAPolymeraseHoloenzymeConsistsoftheCore

EnzymeandSigmaFactor17.6HowDoesRNAPolymeraseFindPromoter

Sequences?17.7TheHoloenzymeGoesThroughTransitionsinthe

ProcessofRecognizingandEscapingfromPromoters

17.8SigmaFactorControlsBindingtoDNAbyRecognizingSpecificSequencesinPromoters

17.9PromoterEfficienciesCanBeIncreasedorDecreasedbyMutation

17.10MultipleRegionsinRNAPolymeraseDirectlyContactPromoterDNA

17.11RNAPolymerase—PromoterandDNA—ProteinInteractionsAretheSameforPromoterRecognitionandDNAMelting

17.12InteractionsBetweenSigmaFactorandCoreRNAPolymeraseChangeDuringPromoterEscape

17.13AModelforEnzymeMovementIsSuggestedbytheCrystalStructure

17.14AStalledRNAPolymeraseCanRestart17.15BacterialRNAPolymeraseTerminatesatDiscrete

Sites17.16HowDoesRhoFactorWork?17.17SupercoilingIsanImportantFeatureofTranscription

17.18PhageT7RNAPolymeraseIsaUsefulModelSystem17.19CompetitionforSigmaFactorsCanRegulateInitiation17.20SigmaFactorsCanBeOrganizedintoCascades17.21SporulationIsControlledbySigmaFactors17.22AntiterminationCanBeaRegulatoryEvent

Chapter18EukaryoticTranscription18.1Introduction18.2EukaryoticRNAPolymerasesConsistofMany

Subunits18.3RNAPolymeraseIHasaBipartitePromoter18.4RNAPolymeraseIIIUsesDownstreamandUpstream

Promoters18.5TheStartPointforRNAPolymeraseII18.6TBPIsaUniversalFactor18.7TheBasalApparatusAssemblesatthePromoter18.8InitiationIsFollowedbyPromoterClearanceand

Elongation18.9EnhancersContainBidirectionalElementsThatAssist

Initiation18.10EnhancersWorkbyIncreasingtheConcentrationof

ActivatorsNearthePromoter18.11GeneExpressionIsAssociatedwithDemethylation18.12CpGIslandsAreRegulatoryTargets

Chapter19RNASplicingandProcessing19.1Introduction19.2The5ʹEndofEukaryoticmRNAIsCapped19.3NuclearSpliceSitesAreShortSequences19.4SpliceSitesAreReadinPairs19.5Pre-mRNASplicingProceedsThroughaLariat

19.6snRNAsAreRequiredforSplicing19.7CommitmentofPre-mRNAtotheSplicingPathway19.8TheSpliceosomeAssemblyPathway19.9AnAlternativeSpliceosomeUsesDifferentsnRNPsto

ProcesstheMinorClassofIntrons19.10Pre-mRNASplicingLikelySharestheMechanismwith

GroupIIAutocatalyticIntrons19.11SplicingIsTemporallyandFunctionallyCoupledwith

MultipleStepsinGeneExpression19.12AlternativeSplicingIsaRule,RatherThanan

Exception,inMulticellularEukaryotes19.13SplicingCanBeRegulatedbyExonicandIntronic

SplicingEnhancersandSilencers19.14trans-SplicingReactionsUseSmallRNAs19.15The3ʹEndsofmRNAsAreGeneratedbyCleavage

andPolyadenylation19.163ʹmRNAEndProcessingIsCriticalforTerminationof

Transcription19.17The3ʹEndFormationofHistonemRNARequiresU7

snRNA19.18tRNASplicingInvolvesCuttingandRejoiningin

SeparateReactions19.19TheUnfoldedProteinResponseIsRelatedtotRNA

Splicing19.20ProductionofrRNARequiresCleavageEventsand

InvolvesSmallRNAs

Chapter20mRNAStabilityandLocalizationEditedbyEllenBaker

20.1Introduction20.2MessengerRNAsAreUnstableMolecules

20.3EukaryoticmRNAsExistintheFormofmRNPsfromTheirBirthtoTheirDeath

20.4ProkaryoticmRNADegradationInvolvesMultipleEnzymes

20.5MostEukaryoticmRNAIsDegradedviaTwoDeadenylation-DependentPathways

20.6OtherDegradationPathwaysTargetSpecificmRNAs20.7mRNA-SpecificHalf-LivesAreControlledby

SequencesorStructuresWithinthemRNA20.8NewlySynthesizedRNAsAreCheckedforDefectsvia

aNuclearSurveillanceSystem20.9QualityControlofmRNATranslationIsPerformedby

CytoplasmicSurveillanceSystems20.10TranslationallySilencedmRNAsAreSequesteredina

VarietyofRNAGranules20.11SomeEukaryoticmRNAsAreLocalizedtoSpecific

RegionsofaCell

Chapter21CatalyticRNAEditedbyDouglasJ.Briant

21.1Introduction21.2GroupIIntronsUndertakeSelf-Splicingby

Transesterification21.3GroupIIntronsFormaCharacteristicSecondary

Structure21.4RibozymesHaveVariousCatalyticActivities21.5SomeGroupIIntronsEncodeEndonucleasesThat

SponsorMobility21.6GroupIIIntronsMayEncodeMultifunctionProteins21.7SomeAutosplicingIntronsRequireMaturases21.8TheCatalyticActivityofRNasePIsDuetoRNA

21.9ViroidsHaveCatalyticActivity21.10RNAEditingOccursatIndividualBases21.11RNAEditingCanBeDirectedbyGuideRNAs21.12ProteinSplicingIsAutocatalytic

Chapter22Translation22.1Introduction22.2TranslationOccursbyInitiation,Elongation,and

Termination22.3SpecialMechanismsControltheAccuracyof

Translation22.4InitiationinBacteriaNeeds30SSubunitsand

AccessoryFactors22.5InitiationInvolvesBasePairingBetweenmRNAand

rRNA22.6ASpecialInitiatortRNAStartsthePolypeptideChain22.7UseoffMet-tRNAfIsControlledbyIF-2andthe

Ribosome22.8SmallSubunitsScanforInitiationSitesonEukaryotic

mRNA22.9EukaryotesUseaComplexofManyInitiationFactors22.10ElongationFactorTuLoadsAminoacyl-tRNAintothe

ASite22.11ThePolypeptideChainIsTransferredtoAminoacyl-

tRNA22.12TranslocationMovestheRibosome22.13ElongationFactorsBindAlternatelytotheRibosome22.14ThreeCodonsTerminateTranslation22.15TerminationCodonsAreRecognizedbyProtein

Factors

22.16RibosomalRNAIsFoundThroughoutBothRibosomalSubunits

22.17RibosomesHaveSeveralActiveCenters22.1816SrRNAPlaysanActiveRoleinTranslation22.1923SrRNAHasPeptidylTransferaseActivity22.20RibosomalStructuresChangeWhentheSubunits

ComeTogether22.21TranslationCanBeRegulated22.22TheCycleofBacterialMessengerRNA

Chapter23UsingtheGeneticCode23.1Introduction23.2RelatedCodonsRepresentChemicallySimilarAmino

Acids23.3Codon—AnticodonRecognitionInvolvesWobbling23.4tRNAsAreProcessedfromLongerPrecursors23.5tRNAContainsModifiedBases23.6ModifiedBasesAffectAnticodon—CodonPairing23.7TheUniversalCodeHasExperiencedSporadic

Alterations23.8NovelAminoAcidsCanBeInsertedatCertainStop

Codons23.9tRNAsAreChargedwithAminoAcidsbyAminoacyl-

tRNASynthetases23.10Aminoacyl-tRNASynthetasesFallintoTwoClasses23.11SynthetasesUseProofreadingtoImproveAccuracy23.12SuppressortRNAsHaveMutatedAnticodonsThat

ReadNewCodons23.13EachTerminationCodonHasNonsenseSuppressors23.14SuppressorsMayCompetewithWild-TypeReadingof

theCode

23.15TheRibosomeInfluencestheAccuracyofTranslation23.16FrameshiftingOccursatSlipperySequences23.17OtherRecodingEvents:TranslationalBypassingand

thetmRNAMechanismtoFreeStalledRibosomes

PARTIVGeneRegulation

Chapter24TheOperonEditedbyLiskinSwint-Kruse

24.1Introduction24.2StructuralGeneClustersAreCoordinatelyControlled24.3ThelacOperonIsNegativeInducible24.4ThelacRepressorIsControlledbyaSmall-Molecule

Inducer24.5cis-ActingConstitutiveMutationsIdentifythe

Operator24.6trans-ActingMutationsIdentifytheRegulatorGene24.7ThelacRepressorIsaTetramerMadeofTwoDimers24.8lacRepressorBindingtotheOperatorIsRegulated

byanAllostericChangeinConformation24.9ThelacRepressorBindstoThreeOperatorsand

InteractswithRNAPolymerase24.10TheOperatorCompeteswithLow-AffinitySitesto

BindRepressor24.11ThelacOperonHasaSecondLayerofControl:

CataboliteRepression24.12ThetrpOperonIsaRepressibleOperonwithThree

TranscriptionUnits24.13ThetrpOperonIsAlsoControlledbyAttenuation24.14AttenuationCanBeControlledbyTranslation24.15StringentControlbyStableRNATranscription

24.16r-ProteinSynthesisIsControlledbyAutoregulation

Chapter25PhageStrategies25.1Introduction25.2LyticDevelopmentIsDividedintoTwoPeriods25.3LyticDevelopmentIsControlledbyaCascade25.4TwoTypesofRegulatoryEventsControltheLytic

Cascade25.5ThePhageT7andT4GenomesShowFunctional

Clustering25.6LambdaImmediateEarlyandDelayedEarlyGenes

AreNeededforBothLysogenyandtheLyticCycle25.7TheLyticCycleDependsonAntiterminationbypN25.8LysogenyIsMaintainedbytheLambdaRepressor

Protein25.9TheLambdaRepressorandItsOperatorsDefinethe

ImmunityRegion25.10TheDNA-BindingFormoftheLambdaRepressorIsa

Dimer25.11TheLambdaRepressorUsesaHelix-Turn-HelixMotif

toBindDNA25.12LambdaRepressorDimersBindCooperativelytothe

Operator25.13TheLambdaRepressorMaintainsanAutoregulatory

Circuit25.14CooperativeInteractionsIncreasetheSensitivityof

Regulation25.15ThecIIandcIIIGenesAreNeededtoEstablish

Lysogeny25.16APoorPromoterRequirescIIProtein25.17LysogenyRequiresSeveralEvents

25.18TheCroRepressorIsNeededforLyticInfection25.19WhatDeterminestheBalanceBetweenLysogenyand

theLyticCycle?

Chapter26EukaryoticTranscriptionRegulation26.1Introduction26.2HowIsaGeneTurnedOn?26.3MechanismofActionofActivatorsandRepressors26.4IndependentDomainsBindDNAandActivate

Transcription26.5TheTwo-HybridAssayDetectsProtein—Protein

Interactions26.6ActivatorsInteractwiththeBasalApparatus26.7ManyTypesofDNA-BindingDomainsHaveBeen

Identified26.8ChromatinRemodelingIsanActiveProcess26.9NucleosomeOrganizationorContentCanBe

ChangedatthePromoter26.10HistoneAcetylationIsAssociatedwithTranscription

Activation26.11MethylationofHistonesandDNAIsConnected26.12PromoterActivationInvolvesMultipleChangesto

Chromatin26.13HistonePhosphorylationAffectsChromatinStructure26.14YeastGALGenes:AModelforActivationand

Repression

Chapter27EpigeneticsIEditedbyTrygveTollefsbol

27.1Introduction27.2HeterochromatinPropagatesfromaNucleationEvent

27.3HeterochromatinDependsonInteractionswithHistones

27.4PolycombandTrithoraxAreAntagonisticRepressorsandActivators

27.5CpGIslandsAreSubjecttoMethylation27.6EpigeneticEffectsCanBeInherited27.7YeastPrionsShowUnusualInheritance

Chapter28EpigeneticsIIEditedbyTrygveTollefsbol

28.1Introduction28.2XChromosomesUndergoGlobalChanges28.3ChromosomeCondensationIsCausedbyCondensins28.4DNAMethylationIsResponsibleforImprinting28.5OppositelyImprintedGenesCanBeControlledbya

SingleCenter28.6PrionsCauseDiseasesinMammals

Chapter29NoncodingRNA29.1Introduction29.2ARiboswitchCanAlterItsStructureAccordingtoIts

Environment29.3NoncodingRNAsCanBeUsedtoRegulateGene

Expression

Chapter30RegulatoryRNA30.1Introduction30.2BacteriaContainRegulatorRNAs30.3MicroRNAsAreWidespreadRegulatorsinEukaryotes30.4HowDoesRNAInterferenceWork?30.5HeterochromatinFormationRequiresMicroRNAs

Glossary

Index


PREFACEOfthediversewaystostudythelivingworld,molecularbiologyhasbeenmostremarkableinthespeedandbreadthofitsexpansion.Newdataareacquireddaily,andnewinsightsintowell-studiedprocessescomeonascalemeasuredinweeksormonthsratherthanyears.It’sdifficulttobelievethatthefirstcompleteorganismalgenomesequencewasobtainedalittleover20yearsago.Thestructureandfunctionofgenesandgenomesandtheirassociatedcellularprocessesaresometimeselegantlyanddeceptivelysimplebutfrequentlyamazinglycomplex,andnosinglebookcandojusticetotherealitiesanddiversitiesofnaturalgeneticsystems.

Thisbookisaimedatadvancedstudentsinmoleculargeneticsandmolecularbiology.Inordertoprovidethemostcurrentunderstandingoftherapidlychangingsubjectsinmolecularbiology,wehaveenlistedleadingscientiststoproviderevisionsandcontentupdatesintheirindividualfieldsofexpertise.Theirexpertknowledgehasbeenincorporatedthroughoutthetext.MuchoftherevisionandreorganizationofthiseditionfollowsthatofthethirdeditionofLewin’sEssentialGENES,buttherearemanyupdatesandfeaturesthatarenewtothisbook.Thiseditionfollowsalogicalflowoftopics;inparticular,discussionofchromatinorganizationandnucleosomestructureprecedesthediscussionofeukaryotictranscription,becausechromosomeorganizationiscriticaltoallDNAtransactionsinthecell,andcurrentresearchinthefieldoftranscriptionalregulationisheavilybiasedtowardthestudyofthe

roleofchromatininthisprocess.Manynewfiguresareincludedinthisbook,somereflectingnewdevelopmentsinthefield,particularlyinthetopicsofchromatinstructureandfunction,epigenetics,andregulationbynoncodingRNAandmicroRNAsineukaryotes.

Thisbookisorganizedintofourparts.PartI(GenesandChromosomes)comprisesChapters1through8.Chapter1servesasanintroductiontothestructureandfunctionofDNAandcontainsbasiccoverageofDNAreplicationandgeneexpression.Chapter2providesinformationonmolecularlaboratorytechniques.Chapter3introducestheinterruptedstructuresofeukaryoticgenes,andChapters4through6discussgenomestructureandevolution.Chapters7and8discussthestructureofeukaryoticchromosomes.

PartII(DNAReplication,Repair,andRecombination)comprisesChapters9through16.Chapters9through12providedetaileddiscussionsofDNAreplicationinplasmids,viruses,andprokaryoticandeukaryoticcells.Chapters13through16coverrecombinationanditsrolesinDNArepairandthehumanimmunesystem,withChapter14discussingDNArepairpathwaysindetailandChapter15focusingondifferenttypesoftransposableelements.

PartIII(TranscriptionandPosttranscriptionalMechanisms)includesChapters17through23.Chapters17and18providemorein-depthcoverageofbacterialandeukaryotictranscription.Chapters19through21areconcernedwithRNA,discussingmessengerRNA,RNAstabilityandlocalization,RNAprocessing,andthecatalyticrolesofRNA.Chapters22and23discusstranslationandthegeneticcode.

PartIV(GeneRegulation)comprisesChapters24through30.InChapter24,theregulationofbacterialgeneexpressionviaoperonsisdiscussed.Chapter25coverstheregulationofexpressionofgenesduringphagedevelopmentastheyinfectbacterialcells.Chapters26through28covereukaryoticgeneregulation,includingepigeneticmodifications.Finally,Chapters29and30coverRNA-basedcontrolofgeneexpressioninprokaryotesandeukaryotes.

ForinstructorswhoprefertoordertopicswiththeessentialsofDNAreplicationandgeneexpressionfollowedbymoreadvancedtopics,thefollowingchaptersequenceissuggested:

Introduction:Chapter1

GeneandGenomeStructure:Chapters4–6

DNAReplication:Chapters9–12

Transcription:Chapters17–20

Translation:Chapters22–23

RegulationofGeneExpression:Chapters7–8and24–30

Otherchapterscanbecoveredattheinstructor’sdiscretion.


THESTUDENTEXPERIENCEThiseditioncontainsseveralfeaturestohelpstudentslearnastheyread:

EachchapterbeginswithaChapterOutlinethatclearlylaysouttheframeworkofthechapterandhelpsstudentsplantheirreadingandstudy.

EachsectionissummarizedwithabulletedlistofKeyConceptstoassiststudentswithdistillingthefocusofeachsection.

GENESXIIincludesthehigh-qualityillustrationsandphotographsthatinstructorsandstudentshavecometoexpectinthisclassictitle.

KeyTermsarehighlightedinboldtypeinthetextandcompiledintheGlossaryattheendofthebook.

EachchapterconcludeswithanexpandedandupdatedlistofReferences,whichprovidesbothprimaryliteratureandcurrentreviewstosupplementandreinforcethechaptercontent.

Additionalonlinestudytoolsareavailableforstudentsandinstructors,includingpracticeactivities,prepopulatedquizzes,andaninteractiveeBookwithWebLinkstorelevantsites,includinganimationsandothermedia.


TEACHINGTOOLSAvarietyofteachingtoolsareavailableviadigitaldownloadandmultipleotherformatstoassistinstructorswithpreparingforandteachingtheircourseswithLewin’sGENESXII:

TheLectureOutlinesinPowerPointformatpresentationpackagedevelopedbyauthorStephenKilpatrickoftheUniversityofPittsburghatJohnstownprovidesoutlinesummariesandrelevantimagesforeachchapterofLewin’sGENESXII.InstructorswithMicrosoftPowerPointsoftwarecancustomizetheoutlines,art,andorderofpresentation.

TheKeyImageReviewprovidestheillustrations,photographs,andtablestowhichJones&BartlettLearningholdsthecopyrightorhaspermissiontoreprintdigitally.Theseimagesarenotforsaleordistributionbutmaybeusedtoenhanceexistingslides,tests,andquizzesorotherclassroommaterial.

TheTestBankhasbeenupdatedandexpandedbyauthorStephenKilpatricktoincludeover1,000questions,inadditiontothe750questionsandactivitiesthatareincludedintheonlinestudyandassessmenttools.Hand-selectedWebLinkstorelevantwebsitesareavailableinalistformatorasdirectlinksintheinteractiveeBook.ThepublisherhaspreparedaTransitionGuidetoassistinstructorswhohaveusedpreviouseditionsofthetextwithconversiontothisnewedition.


AcknowledgmentsTheauthorswouldliketothankthefollowingindividualsfortheirassistanceinthepreparationofthisbook:Theeditorial,production,marketing,andsalesteamsatJones&BartlettLearninghavebeenexemplaryinallaspectsofthisproject.AudreySchwinnandNancyHoffmanndeservespecialmention.

Wethanktheeditorsofindividualchapters,whoseexpertise,enthusiasm,andcarefuljudgmentbroughtthemanuscriptup-to-dateinmanycriticalareas.

JocelynE.Krebs

ElliottS.Goldstein

StephenT.Kilpatrick

Reviewers

TheauthorsandpublisherwouldliketoacknowledgeandthankthefollowingindividualsforservingasreviewersinpreparationforrevisionofLewin’sGENESXII.

HeatherB.Ayala,Ph.D.,GeorgeFoxUniversity

VagnerBenedito,Ph.D.,WestVirginiaUniversity

Cover PageTitle PageCopyright PageDedicationBrief ContentsContentsPrefaceAbout the AuthorsPART I Genes and ChromosomesChapter 1 Genes Are DNA and Encode RNAs and Polypeptides1.1 Introduction1.2 DNA Is the Genetic Material of Bacteria and Viruses1.3 DNA Is the Genetic Material of Eukaryotic Cells1.4 Polynucleotide Chains Have Nitrogenous Bases Linked to a Sugar—Phosphate Backbone1.5 Supercoiling Affects the Structure of DNA1.6 DNA Is a Double Helix1.7 DNA Replication Is Semiconservative1.8 Polymerases Act on Separated DNA Strands at the Replication Fork1.9 Genetic Information Can Be Provided by DNA or RNA1.10 Nucleic Acids Hybridize by Base Pairing1.11 Mutations Change the Sequence of DNA1.12 Mutations Can Affect Single Base Pairs or Longer Sequences1.13 The Effects of Mutations Can Be Reversed1.14 Mutations Are Concentrated at Hotspots1.15 Many Hotspots Result from Modified Bases1.16 Some Hereditary Agents Are Extremely Small1.17 Most Genes Encode Polypeptides1.18 Mutations in the Same Gene Cannot Complement1.19 Mutations May Cause Loss of Function or Gain of Function1.20 A Locus Can Have Many Different Mutant Alleles1.21 A Locus Can Have More Than One Wild-Type Allele1.22 Recombination Occurs by Physical Exchange of DNA1.23 The Genetic Code Is Triplet1.24 Every Coding Sequence Has Three Possible Reading Frames1.25 Bacterial Genes Are Colinear with Their Products1.26 Several Processes Are Required to Express the Product of a Gene1.27 Proteins Are trans-Acting but Sites on DNA Are cis-Acting

Chapter 2 Methods in Molecular Biology and Genetic Engineering2.1 Introduction2.2 Nucleases2.3 Cloning2.4 Cloning Vectors Can Be Specialized for Different Purposes2.5 Nucleic Acid Detection2.6 DNA Separation Techniques2.7 DNA Sequencing2.8 PCR and RT-PCR2.9 Blotting Methods2.10 DNA Microarrays2.11 Chromatin Immunoprecipitation2.12 Gene Knockouts, Transgenics, and Genome Editing

Chapter 3 The Interrupted Gene3.1 Introduction3.2 An Interrupted Gene Has Exons and Introns3.3 Exon and Intron Base Compositions Differ3.4 Organization of Interrupted Genes Can Be Conserved3.5 Exon Sequences Under Negative Selection Are Conserved but Introns Vary3.6 Exon Sequences Under Positive Selection Vary but Introns Are Conserved3.7 Genes Show a Wide Distribution of Sizes Due Primarily to Intron Size and Number Variation3.8 Some DNA Sequences Encode More Than One Polypeptide3.9 Some Exons Correspond to Protein Functional Domains3.10 Members of a Gene Family Have a Common Organization3.11 There Are Many Forms of Information in DNA

Chapter 4 The Content of the Genome4.1 Introduction4.2 Genome Mapping Reveals That Individual Genomes Show Extensive Variation4.3 SNPs Can Be Associated with Genetic Disorders4.4 Eukaryotic Genomes Contain Nonrepetitive and Repetitive DNA Sequences4.5 Eukaryotic Protein-Coding Genes Can Be Identified by the Conservation of Exons and of Genome Organization4.6 Some Eukaryotic Organelles Have DNA4.7 Organelle Genomes Are Circular DNAs That Encode Organelle Proteins4.8 The Chloroplast Genome Encodes Many Proteins and RNAs4.9 Mitochondria and Chloroplasts Evolved by Endosymbiosis

Chapter 5 Genome Sequences and Evolution5.1 Introduction5.2 Prokaryotic Gene Numbers Range Over an Order of Magnitude5.3 Total Gene Number Is Known for Several Eukaryotes5.4 How Many Different Types of Genes Are There?5.5 The Human Genome Has Fewer Genes Than Originally Expected5.6 How Are Genes and Other Sequences Distributed in the Genome?5.7 The Y Chromosome Has Several Male-Specific Genes5.8 How Many Genes Are Essential?5.9 About 10,000 Genes Are Expressed at Widely Differing Levels in a Eukaryotic Cell5.10 Expressed Gene Number Can Be Measured En Masse5.11 DNA Sequences Evolve by Mutation and a Sorting Mechanism5.12 Selection Can Be Detected by Measuring Sequence Variation5.13 A Constant Rate of Sequence Divergence Is a Molecular Clock5.14 The Rate of Neutral Substitution Can Be Measured from Divergence of Repeated Sequences5.15 How Did Interrupted Genes Evolve?5.16 Why Are Some Genomes So Large?5.17 Morphological Complexity Evolves by Adding New Gene Functions5.18 Gene Duplication Contributes to Genome Evolution5.19 Globin Clusters Arise by Duplication and Divergence5.20 Pseudogenes Have Lost Their Original Functions5.21 Genome Duplication Has Played a Role in Plant and Vertebrate Evolution5.22 What Is the Role of Transposable Elements in Genome Evolution5.23 There Can Be Biases in Mutation, Gene Conversion, and Codon Usage

Chapter 6 Clusters and Repeats6.1 Introduction6.2 Unequal Crossing-Over Rearranges Gene Clusters6.3 Genes for rRNA Form Tandem Repeats Including an Invariant Transcription Unit6.4 Crossover Fixation Could Maintain Identical Repeats6.5 Satellite DNAs Often Lie in Heterochromatin6.6 Arthropod Satellites Have Very Short Identical Repeats6.7 Mammalian Satellites Consist of Hierarchical Repeats6.8 Minisatellites Are Useful for DNA Profiling

Chapter 7 Chromosomes7.1 Introduction7.2 Viral Genomes Are Packaged into Their Coats7.3 The Bacterial Genome Is a Nucleoid with Dynamic Structural Properties7.4 The Bacterial Genome Is Supercoiled and Has Four Macrodomains7.5 Eukaryotic DNA Has Loops and Domains Attached to a Scaffold7.6 Specific Sequences Attach DNA to an Interphase Matrix7.7 Chromatin Is Divided into Euchromatin and Heterochromatin7.8 Chromosomes Have Banding Patterns7.9 Lampbrush Chromosomes Are Extended7.10 Polytene Chromosomes Form Bands7.11 Polytene Chromosomes Expand at Sites of Gene Expression7.12 The Eukaryotic Chromosome Is a Segregation Device7.13 Regional Centromeres Contain a Centromeric Histone H3 Variant and Repetitive DNA7.14 Point Centromeres in S. cerevisiae Contain Short, Essential DNA Sequences7.15 The S. cerevisiae Centromere Binds a Protein Complex7.16 Telomeres Have Simple Repeating Sequences7.17 Telomeres Seal the Chromosome Ends and Function in Meiotic Chromosome Pairing7.18 Telomeres Are Synthesized by a Ribonucleoprotein Enzyme7.19 Telomeres Are Essential for Survival

Chapter 8 Chromatin8.1 Introduction8.2 DNA Is Organized in Arrays of Nucleosomes8.3 The Nucleosome Is the Subunit of All Chromatin8.4 Nucleosomes Are Covalently Modified8.5 Histone Variants Produce Alternative Nucleosomes8.6 DNA Structure Varies on the Nucleosomal Surface8.7 The Path of Nucleosomes in the Chromatin Fiber8.8 Replication of Chromatin Requires Assembly of Nucleosomes8.9 Do Nucleosomes Lie at Specific Positions?8.10 Nucleosomes Are Displaced and Reassembled During Transcription8.11 DNase Sensitivity Detects Changes in Chromatin Structure8.12 An LCR Can Control a Domain8.13 Insulators Define Transcriptionally Independent Domains

PART II DNA Replication and RecombinationChapter 9 Replication Is Connected to the Cell Cycle9.1 Introduction9.2 Bacterial Replication Is Connected to the Cell Cycle9.3 The Shape and Spatial Organization of a Bacterium Are Important During Chromosome Segregation and Cell Division9.4 Mutations in Division or Segregation Affect Cell Shape9.5 FtsZ Is Necessary for Septum Formation9.6 min and noc/slm Genes Regulate the Location of the Septum9.7 Partition Involves Separation of the Chromosomes9.8 Chromosomal Segregation Might Require Site-Specific Recombination9.9 The Eukaryotic Growth Factor Signal Transduction Pathway Promotes Entry to S Phase9.10 Checkpoint Control for Entry into S Phase: p53, a Guardian of the Checkpoint9.11 Checkpoint Control for Entry into S Phase: Rb, a Guardian of the Checkpoint

Chapter 10 The Replicon: Initiation of Replication10.1 Introduction10.2 An Origin Usually Initiates Bidirectional Replication10.3 The Bacterial Genome Is (Usually) a Single Circular Replicon10.4 Methylation of the Bacterial Origin Regulates Initiation10.5 Initiation: Creating the Replication Forks at the Origin oriC10.6 Multiple Mechanisms Exist to Prevent Premature Reinitiation of Replication10.7 Archaeal Chromosomes Can Contain Multiple Replicons10.8 Each Eukaryotic Chromosome Contains Many Replicons10.9 Replication Origins Can Be Isolated in Yeast10.10 Licensing Factor Controls Eukaryotic Rereplication10.11 Licensing Factor Binds to ORC

Chapter 11 DNA Replication11.1 Introduction11.2 DNA Polymerases Are the Enzymes That Make DNA11.3 DNA Polymerases Have Various Nuclease Activities11.4 DNA Polymerases Control the Fidelity of Replication11.5 DNA Polymerases Have a Common Structure11.6 The Two New DNA Strands Have Different Modes of Synthesis11.7 Replication Requires a Helicase and a Single-Stranded Binding Protein11.8 Priming Is Required to Start DNA Synthesis11.9 Coordinating Synthesis of the Lagging and Leading Strands11.10 DNA Polymerase Holoenzyme Consists of Subcomplexes11.11 The Clamp Controls Association of Core Enzyme with DNA11.12 Okazaki Fragments Are Linked by Ligase11.13 Separate Eukaryotic DNA Polymerases Undertake Initiation and Elongation11.14 Lesion Bypass Requires Polymerase Replacement11.15 Termination of Replication

Chapter 12 Extrachromosomal Replicons12.1 Introduction12.2 The Ends of Linear DNA Are a Problem for Replication12.3 Terminal Proteins Enable Initiation at the Ends of Viral DNAs12.4 Rolling Circles Produce Multimers of a Replicon12.5 Rolling Circles Are Used to Replicate Phage Genomes12.6 The F Plasmid Is Transferred by Conjugation Between Bacteria12.7 Conjugation Transfers Single-Stranded DNA12.8 Single-Copy Plasmids Have a Partitioning System12.9 Plasmid Incompatibility Is Determined by the Replicon12.10 The ColE1 Compatibility System Is Controlled by an RNA Regulator12.11 How Do Mitochondria Replicate and Segregate?12.12 D Loops Maintain Mitochondrial Origins12.13 The Bacterial Ti Plasmid Causes Crown Gall Disease in Plants12.14 T-DNA Carries Genes Required for Infection12.15 Transfer of T-DNA Resembles Bacterial Conjugation

Chapter 13 Homologous and Site-Specific Recombination13.1 Introduction13.2 Homologous Recombination Occurs Between Synapsed Chromosomes in Meiosis13.3 Double-Strand Breaks Initiate Recombination13.4 Gene Conversion Accounts for Interallelic Recombination13.5 The Synthesis-Dependent Strand-Annealing Model13.6 The Single-Strand Annealing Mechanism Functions at Some Double-Strand Breaks13.7 Break-Induced Replication Can Repair Double-Strand Breaks13.8 Recombining Meiotic Chromosomes Are Connected by the Synaptonemal Complex13.9 The Synaptonemal Complex Forms After Double-Strand Breaks13.10 Pairing and Synaptonemal Complex Formation Are Independent13.11 The Bacterial RecBCD System Is Stimulated by chi Sequences13.12 Strand-Transfer Proteins Catalyze Single-Strand Assimilation13.13 Holliday Junctions Must Be Resolved13.14 Eukaryotic Genes Involved in Homologous Recombination1. End Processing/Presynapsis2. Synapsis3. DNA Heteroduplex Extension and Branch Migration4. Resolution

13.15 Specialized Recombination Involves Specific Sites13.16 Site-Specific Recombination Involves Breakage and Reunion13.17 Site-Specific Recombination Resembles Topoisomerase Activity13.18 Lambda Recombination Occurs in an Intasome13.19 Yeast Can Switch Silent and Active Mating-Type Loci13.20 Unidirectional Gene Conversion Is Initiated by the Recipient MAT Locus13.21 Antigenic Variation in Trypanosomes Uses Homologous Recombination13.22 Recombination Pathways Adapted for Experimental Systems

Chapter 14 Repair Systems14.1 Introduction14.2 Repair Systems Correct Damage to DNA14.3 Excision Repair Systems in E. coli14.4 Eukaryotic Nucleotide Excision Repair Pathways14.5 Base Excision Repair Systems Require Glycosylases14.6 Error-Prone Repair and Translesion Synthesis14.7 Controlling the Direction of Mismatch Repair14.8 Recombination-Repair Systems in E. coli14.9 Recombination Is an Important Mechanism to Recover from Replication Errors14.10 Recombination-Repair of Double-Strand Breaks in Eukaryotes14.11 Nonhomologous End Joining Also Repairs Double-Strand Breaks14.12 DNA Repair in Eukaryotes Occurs in the Context of Chromatin14.13 RecA Triggers the SOS System

Chapter 15 Transposable Elements and Retroviruses15.1 Introduction15.2 Insertion Sequences Are Simple Transposition Modules15.3 Transposition Occurs by Both Replicative and Nonreplicative Mechanisms15.4 Transposons Cause Rearrangement of DNA15.5 Replicative Transposition Proceeds Through a Cointegrate15.6 Nonreplicative Transposition Proceeds by Breakage and Reunion15.7 Transposons Form Superfamilies and Families15.8 The Role of Transposable Elements in Hybrid Dysgenesis15.9 P Elements Are Activated in the Germline15.10 The Retrovirus Life Cycle Involves Transposition-Like Events15.11 Retroviral Genes Code for Polyproteins15.12 Viral DNA Is Generated by Reverse Transcription15.13 Viral DNA Integrates into the Chromosome15.14 Retroviruses May Transduce Cellular Sequences15.15 Retroelements Fall into Three Classes15.16 Yeast Ty Elements Resemble Retroviruses15.17 The Alu Family Has Many Widely Dispersed Members15.18 LINEs Use an Endonuclease to Generate a Priming End

Chapter 16 Somatic DNA Recombination and Hypermutation in the Immune System16.1 The Immune System: Innate and Adaptive Immunity16.2 The Innate Response Utilizes Conserved Recognition Molecules and Signaling Pathways16.3 Adaptive Immunity16.4 Clonal Selection Amplifies Lymphocytes That Respond to a Given Antigen16.5 Ig Genes Are Assembled from Discrete DNA Segments in B Lymphocytes16.6 L Chains Are Assembled by a Single Recombination Event16.7 H Chains Are Assembled by Two Sequential Recombination Events16.8 Recombination Generates Extensive Diversity16.9 V(D)J DNA Recombination Relies on RSS and Occurs by Deletion or Inversion16.10 Allelic Exclusion Is Triggered by Productive Rearrangements16.11 RAG1/RAG2 Catalyze Breakage and Religation of V(D)J Gene Segments16.12 B Cell Development in the Bone Marrow: From Common Lymphoid Progenitor to Mature B Cell16.13 Class Switch DNA Recombination16.14 CSR Involves AID and Elements of the NHEJ Pathway16.15 Somatic Hypermutation Generates Additional Diversity and Provides the Substrate for Higher-Affinity Submutants16.16 SHM Is Mediated by AID, Ung, Elements of the Mismatch DNA Repair Machinery, and Translesion DNA Synthesis Polymerases16.17 Igs Expressed in Avians Are Assembled from Pseudogenes16.18 Chromatin Architecture Dynamics of the IgH Locus in V(D)J Recombination, CSR, and SHM16.19 Epigenetics of V(D)J Recombination, CSR, and SHM16.20 B Cell Differentiation Results in Maturation of the Antibody Response and Generation of Long-lived Plasma Cells and Memory B Cells16.21 The T Cell Receptor Antigen Is Related to the BCR16.22 The TCR Functions in Conjunction with the MHC16.23 The MHC Locus Comprises a Cohort of Genes Involved in Immune Recognition

PART III Transcription and Posttranscriptional MechanismsChapter 17 Prokaryotic Transcription17.1 Introduction17.2 Transcription Occurs by Base Pairing in a "Bubble" of Unpaired DNA17.3 The Transcription Reaction Has Three Stages17.4 Bacterial RNA Polymerase Consists of Multiple Subunits17.5 RNA Polymerase Holoenzyme Consists of the Core Enzyme and Sigma Factor17.6 How Does RNA Polymerase Find Promoter Sequences?17.7 The Holoenzyme Goes Through Transitions in the Process of Recognizing and Escaping from Promoters17.8 Sigma Factor Controls Binding to DNA by Recognizing Specific Sequences in Promoters17.9 Promoter Efficiencies Can Be Increased or Decreased by Mutation17.10 Multiple Regions in RNA Polymerase Directly Contact Promoter DNA17.11 RNA Polymerase—Promoter and DNA—Protein Interactions Are the Same for Promoter Recognition and DNA Melting17.12 Interactions Between Sigma Factor and Core RNA Polymerase Change During Promoter Escape17.13 A Model for Enzyme Movement Is Suggested by the Crystal Structure17.14 A Stalled RNA Polymerase Can Restart17.15 Bacterial RNA Polymerase Terminates at Discrete Sites17.16 How Does Rho Factor Work?17.17 Supercoiling Is an Important Feature of Transcription17.18 Phage T7 RNA Polymerase Is a Useful Model System17.19 Competition for Sigma Factors Can Regulate Initiation17.20 Sigma Factors Can Be Organized into Cascades17.21 Sporulation Is Controlled by Sigma Factors17.22 Antitermination Can Be a Regulatory Event

Chapter 18 Eukaryotic Transcription18.1 Introduction18.2 Eukaryotic RNA Polymerases Consist of Many Subunits18.3 RNA Polymerase I Has a Bipartite Promoter18.4 RNA Polymerase III Uses Downstream and Upstream Promoters18.5 The Start Point for RNA Polymerase II18.6 TBP Is a Universal Factor18.7 The Basal Apparatus Assembles at the Promoter18.8 Initiation Is Followed by Promoter Clearance and Elongation18.9 Enhancers Contain Bidirectional Elements That Assist Initiation18.10 Enhancers Work by Increasing the Concentration of Activators Near the Promoter18.11 Gene Expression Is Associated with Demethylation18.12 CpG Islands Are Regulatory Targets

Chapter 19 RNA Splicing and Processing19.1 Introduction19.2 The 5ʹ End of Eukaryotic mRNA Is Capped19.3 Nuclear Splice Sites Are Short Sequences19.4 Splice Sites Are Read in Pairs19.5 Pre-mRNA Splicing Proceeds Through a Lariat19.6 snRNAs Are Required for Splicing19.7 Commitment of Pre-mRNA to the Splicing Pathway19.8 The Spliceosome Assembly Pathway19.9 An Alternative Spliceosome Uses Different snRNPs to Process the Minor Class of Introns19.10 Pre-mRNA Splicing Likely Shares the Mechanism with Group II Autocatalytic Introns19.11 Splicing Is Temporally and Functionally Coupled with Multiple Steps in Gene Expression19.12 Alternative Splicing Is a Rule, Rather Than an Exception, in Multicellular Eukaryotes19.13 Splicing Can Be Regulated by Exonic and Intronic Splicing Enhancers and Silencers19.14 trans-Splicing Reactions Use Small RNAs19.15 The 3ʹ Ends of mRNAs Are Generated by Cleavage and Polyadenylation19.16 3ʹ mRNA End Processing Is Critical for Termination of Transcription19.17 The 3ʹ End Formation of Histone mRNA Requires U7 snRNA19.18 tRNA Splicing Involves Cutting and Rejoining in Separate Reactions19.19 The Unfolded Protein Response Is Related to tRNA Splicing19.20 Production of rRNA Requires Cleavage Events and Involves Small RNAs

Chapter 20 mRNA Stability and Localization20.1 Introduction20.2 Messenger RNAs Are Unstable Molecules20.3 Eukaryotic mRNAs Exist in the Form of mRNPs from Their Birth to Their Death20.4 Prokaryotic mRNA Degradation Involves Multiple Enzymes20.5 Most Eukaryotic mRNA Is Degraded via Two Deadenylation-Dependent Pathways20.6 Other Degradation Pathways Target Specific mRNAs20.7 mRNA-Specific Half-Lives Are Controlled by Sequences or Structures Within the mRNA20.8 Newly Synthesized RNAs Are Checked for Defects via a Nuclear Surveillance System20.9 Quality Control of mRNA Translation Is Performed by Cytoplasmic Surveillance Systems20.10 Translationally Silenced mRNAs Are Sequestered in a Variety of RNA Granules20.11 Some Eukaryotic mRNAs Are Localized to Specific Regions of a Cell

Chapter 21 Catalytic RNA21.1 Introduction21.2 Group I Introns Undertake Self-Splicing by Transesterification21.3 Group I Introns Form a Characteristic Secondary Structure21.4 Ribozymes Have Various Catalytic Activities21.5 Some Group I Introns Encode Endonucleases That Sponsor Mobility21.6 Group II Introns May Encode Multifunction Proteins21.7 Some Autosplicing Introns Require Maturases21.8 The Catalytic Activity of RNase P Is Due to RNA21.9 Viroids Have Catalytic Activity21.10 RNA Editing Occurs at Individual Bases21.11 RNA Editing Can Be Directed by Guide RNAs21.12 Protein Splicing Is Autocatalytic

Chapter 22 Translation22.1 Introduction22.2 Translation Occurs by Initiation, Elongation, and Termination22.3 Special Mechanisms Control the Accuracy of Translation22.4 Initiation in Bacteria Needs 30S Subunits and Accessory Factors22.5 Initiation Involves Base Pairing Between mRNA and rRNA22.6 A Special Initiator tRNA Starts the Polypeptide Chain22.7 Use of fMet-tRNAf Is Controlled by IF-2 and the Ribosome22.8 Small Subunits Scan for Initiation Sites on Eukaryotic mRNA22.9 Eukaryotes Use a Complex of Many Initiation Factors22.10 Elongation Factor Tu Loads Aminoacyl-tRNA into the A Site22.11 The Polypeptide Chain Is Transferred to Aminoacyl-tRNA22.12 Translocation Moves the Ribosome22.13 Elongation Factors Bind Alternately to the Ribosome22.14 Three Codons Terminate Translation22.15 Termination Codons Are Recognized by Protein Factors22.16 Ribosomal RNA Is Found Throughout Both Ribosomal Subunits22.17 Ribosomes Have Several Active Centers22.18 16S rRNA Plays an Active Role in Translation22.19 23S rRNA Has Peptidyl Transferase Activity22.20 Ribosomal Structures Change When the Subunits Come Together22.21 Translation Can Be Regulated22.22 The Cycle of Bacterial Messenger RNA

Chapter 23 Using the Genetic Code23.1 Introduction23.2 Related Codons Represent Chemically Similar Amino Acids23.3 Codon—Anticodon Recognition Involves Wobbling23.4 tRNAs Are Processed from Longer Precursors23.5 tRNA Contains Modified Bases23.6 Modified Bases Affect Anticodon—Codon Pairing23.7 The Universal Code Has Experienced Sporadic Alterations23.8 Novel Amino Acids Can Be Inserted at Certain Stop Codons23.9 tRNAs Are Charged with Amino Acids by Aminoacyl-tRNA Synthetases23.10 Aminoacyl-tRNA Synthetases Fall into Two Classes23.11 Synthetases Use Proofreading to Improve Accuracy23.12 Suppressor tRNAs Have Mutated Anticodons That Read New Codons23.13 Each Termination Codon Has Nonsense Suppressors23.14 Suppressors May Compete with Wild-Type Reading of the Code23.15 The Ribosome Influences the Accuracy of Translation23.16 Frameshifting Occurs at Slippery Sequences23.17 Other Recoding Events: Translational Bypassing and the tmRNA Mechanism to Free Stalled Ribosomes

PART IV Gene RegulationChapter 24 The Operon24.1 Introduction24.2 Structural Gene Clusters Are Coordinately Controlled24.3 The lac Operon Is Negative Inducible24.4 The lac Repressor Is Controlled by a Small-Molecule Inducer24.5 cis-Acting Constitutive Mutations Identify the Operator24.6 trans-Acting Mutations Identify the Regulator Gene24.7 The lac Repressor Is a Tetramer Made of Two Dimers24.8 lac Repressor Binding to the Operator Is Regulated by an Allosteric Change in Conformation24.9 The lac Repressor Binds to Three Operators and Interacts with RNA Polymerase24.10 The Operator Competes with Low-Affinity Sites to Bind Repressor24.11 The lac Operon Has a Second Layer of Control: Catabolite Repression24.12 The trp Operon Is a Repressible Operon with Three Transcription Units24.13 The trp Operon Is Also Controlled by Attenuation24.14 Attenuation Can Be Controlled by Translation24.15 Stringent Control by Stable RNA Transcription24.16 r-Protein Synthesis Is Controlled by Autoregulation

Chapter 25 Phage Strategies25.1 Introduction25.2 Lytic Development Is Divided into Two Periods25.3 Lytic Development Is Controlled by a Cascade25.4 Two Types of Regulatory Events Control the Lytic Cascade25.5 The Phage T7 and T4 Genomes Show Functional Clustering25.6 Lambda Immediate Early and Delayed Early Genes Are Needed for Both Lysogeny and the Lytic Cycle25.7 The Lytic Cycle Depends on Antitermination by pN25.8 Lysogeny Is Maintained by the Lambda Repressor Protein25.9 The Lambda Repressor and Its Operators Define the Immunity Region25.10 The DNA-Binding Form of the Lambda Repressor Is a Dimer25.11 The Lambda Repressor Uses a Helix-Turn-Helix Motif to Bind DNA25.12 Lambda Repressor Dimers Bind Cooperatively to the Operator25.13 The Lambda Repressor Maintains an Autoregulatory Circuit25.14 Cooperative Interactions Increase the Sensitivity of Regulation25.15 The cII and cIII Genes Are Needed to Establish Lysogeny25.16 A Poor Promoter Requires cII Protein25.17 Lysogeny Requires Several Events25.18 The Cro Repressor Is Needed for Lytic Infection25.19 What Determines the Balance Between Lysogeny and the Lytic Cycle?

Chapter 26 Eukaryotic Transcription Regulation26.1 Introduction26.2 How Is a Gene Turned On?26.3 Mechanism of Action of Activators and Repressors26.4 Independent Domains Bind DNA and Activate Transcription26.5 The Two-Hybrid Assay Detects Protein—Protein Interactions26.6 Activators Interact with the Basal Apparatus26.7 Many Types of DNA-Binding Domains Have Been Identified26.8 Chromatin Remodeling Is an Active Process26.9 Nucleosome Organization or Content Can Be Changed at the Promoter26.10 Histone Acetylation Is Associated with Transcription Activation26.11 Methylation of Histones and DNA Is Connected26.12 Promoter Activation Involves Multiple Changes to Chromatin26.13 Histone Phosphorylation Affects Chromatin Structure26.14 Yeast GAL Genes: A Model for Activation and Repression

Chapter 27 Epigenetics I27.1 Introduction27.2 Heterochromatin Propagates from a Nucleation Event27.3 Heterochromatin Depends on Interactions with Histones27.4 Polycomb and Trithorax Are Antagonistic Repressors and Activators27.5 CpG Islands Are Subject to Methylation27.6 Epigenetic Effects Can Be Inherited27.7 Yeast Prions Show Unusual Inheritance

Chapter 28 Epigenetics II28.1 Introduction28.2 X Chromosomes Undergo Global Changes28.3 Chromosome Condensation Is Caused by Condensins28.4 DNA Methylation Is Responsible for Imprinting28.5 Oppositely Imprinted Genes Can Be Controlled by a Single Center28.6 Prions Cause Diseases in Mammals

Chapter 29 Noncoding RNA29.1 Introduction29.2 A Riboswitch Can Alter Its Structure According to Its Environment29.3 Noncoding RNAs Can Be Used to Regulate Gene Expression

Chapter 30 Regulatory RNA30.1 Introduction30.2 Bacteria Contain Regulator RNAs30.3 MicroRNAs Are Widespread Regulators in Eukaryotes30.4 How Does RNA Interference Work?30.5 Heterochromatin Formation Requires MicroRNAs

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LEWIN’S GENES XII · 2020. 4. 19. · Names: Krebs, Jocelyn E., author. | Goldstein, Elliott S., author. | Kilpatrick, Stephen T., author. Title: Lewin’s genes XII Other titles: