第9章细胞分裂周期减数分裂

ChapterChapter9CellCycleandCellOverviewoftheCellSMControlofcellnumberandcellCellcycle:reproductivecycleofthecell:theorderlysequenceofeventsbywhichacellduplicatesitscontentsanddividesintotwo.Itistheessentialmechanismbywhichalllivingthingsreproduce.Cellsreproducebyduplicatingtheircontentsanddividingintwo,aprocesscalledthecelldivisioncycle,orcellcycle9.19.1OverviewoftheCellThecellcycleisdividedintofourPeriodduringaPeriodduringainwhichDNAisGap1phaseoftheeucaryoticcellcycle,betweentheendofcytokinesisandthestartofDNAsynthesis.Gap2phaseofthebetweentheendofDNAsynthesisandthestartofmitosis.cellduringwhichthenucleusandcytoplasmdivide.about0.5-1hr.cleavagedivision卵裂:Inanimalembryos,ifinterphaselastedonlylongenoughforDNAreplication,thecellwouldnothavetimetodoubleitsmassbeforeitdividedandwouldconsequentlyshrinkwitheachdivision.condensation:thefirstvisiblesignthatacellisabouttoenterMphaseistheprogressivecondensationofitschromosomes.Figure.MolecularBiologyoftheCell(©GarlandScienceAcell-cyclecontrolsystemtriggersthemajorprocessesofthecellcycleCheckpoints:pointintheeucaryoticcell-divisioncyclewhereprogressthroughthecyclecanbehalteduntilconditionsaresuitableforthecelltoproceedtothenextstage.Three

G1:regulationofcellnumbersespecialimportantG0:nervecells,skeletalmuscleCheckpointsinthecell-cyclecontrolsystemensurethatkeyprocessesinthecycleoccurintheproperstartFigure.EssentialCellBiology(©GarlandScienceCell-cyclecontrolissimilarinallTheproteinsofthecell-cyclecontrolsystemfirstappearedmorethanabillionyearsago,andtheyhavebeensowellconservedoverthecourseofevolutionthatmanyofthemfunctionperfectlywhentransferredfromahumancelltoayeast.Studyingthecellcycleinacell-free9.29.2TheCell-CycleControlTwotypesofmachineryareinvolvedincell①ManufacturesthenewcomponentsofthegrowingHaulsthecomponentsintotheircorrectplacesandpartitionsthemappropriatelywhenthecelldividesintwo.Cell-CycleControlSystem:networkofregulatoryproteinsthatgovernsprogressionofaeucaryoticcellthroughthecellcycle.Thecell-cyclecontrolsystemdependsoncyclicallyactivatedproteinkinasescalledCdksProtein:phosphorylation----proteinkinasescyclins细胞周期蛋白：Proteinthatperiodicallyrisesandfallsinconcentrationinstepwiththeeucaryoticcellcycle.Cyclinsactivatespecificproteinkinaseandtherebyhelpcontrolprogressionfromonestageofcellcycletonext.Cyclin-dependentproteinProteinkinasesthathastobecomplexedwithacyclinproteininordertoact.DifferentCdk-cyclincomplexestriggerdifferentstepsinthecell-divisioncyclebyphosphorylatingspecifictargetproteins.Progressionthroughthecellcycledependsoncyclin-dependentproteinkinases(Cdks)①②CyclinhelpsdirecttheCdktothetargetproteinsthattheCdkTheaccumulationofcyclinsregulatestheactivityofCdksCyclins-Cdkcomplexesofthecell-cyclecontrolsystemFigure.MolecularBiologyoftheCell(©GarlandScienceHowWeDiscoveryofcyclinsand Backtotheegg arrestedatastageintheAmatureXenopus爪蟾蜍eggprovidesaconvenientsystemforstudyingcelldivisioncleavagedivision卵裂----nocellgrowth,andallthecellsoftheembryodividesynchronously同GiveusanAmaturationpromotingfactor(MPF)activitywasdiscoveredbyinjectingXenopuseggcytoplasmintoXenopusoocytes卵母细胞Theactivity(MPF)ofduringthecellcycleinFishinginCyclinisacomponentofMPFiscalledM- Mcyclin—regulatorysubunitMitoticcdk—catalyticsubunitAllintheManyofthecell-cyclecontrolgeneshavechangedsolittleduringevolutionthatthehumanversionofthegenewillfunctionperfectlywellinayeastcell.Whetheryeast,animal,orplantuseessentiallythesamemoleculestocontroltheeventsoftheircellCell-cyclecontrolcanbedissectedgeneticallybyanalysisofyeastmutants.Theyeastshavetheabilitytoproliferateinahaploidstate,withonlyasinglecopyofeachgenepresentinthecell.AcomparisonofthecellcyclesoffissionItdosenotbreakdownduringMItdosenothaveanormalG2Thebehaviorofatemperature-sensitiveCdc--lateMThemorphology形态学ofbuddingyeast--lateMnormalcell—budsvaryin Cdc15mutantcell—uniformlywithTheactivityofCdksisalsoregulatedbyphosphorlationanddephosphorylationForaCdktobeactive,itmustbephosphorylatedatonesiteanddephosphorylatedattwoothersites Differentcyclin-Cdkcomplexestriggerdifferentstepsinthecellcycle

ScyclinsG1cyclinsFigure.MolecularBiologyoftheCell(©GarlandScienceCyclinconcentrationareregulatedbytranscriptionandbyproteolysisDistinctCdksassociatewithdifferentcyclinstotriggerthedifferneteventsofthecellcycleTheactivityofCdksisregulatedbycyclinThestructuralbasisofCdkThecontrolofproteolysisbyAPC/Canaphasepromotingcomplex,cyclosome细胞周期体)duringthecellcycleThecontrolofproteolysisbySCF(skp1-cullin-F-boxprotein)duringthecellcycleCdkActivitycanbeblockedbyCdkinhibitorCdkinhibitorproteins:proteinthatinhibitscyclin-Cdkcomplexes,primarilytoinhibitprogressthroughtheG1andSphasesofthecellcycle.Suchasp21. Mostofthediversityincell-divisionratesintheadultbodylinesinthevariationinthetimethatcellsspendinG0orinG1.livercells>manycells>epithelial escapefromtheG1checkpointorfromG0requirestheaccumulationofG1cyclins,andmitogens有丝分裂原functionbystimulatingthisaccumulation.TheactivityofaCdkcanbeblockedbythebindingofaCdkinhibitorAcheckpointinG1offersthecellaThecell-cyclecontrolsystemcanpausethecycleatvariouscheckpointsTrueorFalseandTheregulationofcyclin-Cdkcomplexesdependsentirelyonphosphorylationanddephosphorylation.TrueorFalseandTheregulationofcyclin-Cdkcomplexesdependsentirelyonphosphorylationanddephosphorylation.Althoughcyclin–Cdkcomplexesareindeedregulatedbyphosphorylationanddephosphorylation,theycanalsoberegulatedbythebindingofCdkinhibitorproteins.Moreover,theratesofsynthesisandproteolysisofthecyclinsubunitsareextremelyimportantforregulatingCdkactivity.9.39.3S S-CdkinitiatesDNAreplicationandhelpsblocklargeproteincomplexthatisboundtotheDNAatoriginsofreplicationineucaryoticchromosomesthroughoutthecellcycle.cdc6:WhenitbindstoORCinG1,itpromotesthebinding additionalproteinstoformapre-replativcomplex.S-Cdk:ItinitiatesoriginIthelpspreventre-repelicationoftheControlofchromosomeEnsuretheeachoriginisactivatedonlyonceineachcellcycleFigure.MolecularBiologyoftheCell(©GarlandScienceS-CdktriggersDNArepelicationandensuresthatDNArepelicationisinitiatedonlyoncepercellcycleFigure.EssentialCellBiology(©GarlandScienceControloftheinitiationofDNAFigure.MolecularBiologyoftheCell(©GarlandScienceholdthesisterchromatidsofeachreplicatedchromosometogetherThiscohesionbetweensisterchromatidsiscrucialforproperchromosomesegregation,anditisbrokencompletelyonlyinlatemitosistoallowthesisterchromatidstobepulledapartbythemitoticspindle.Figure.EssentialCellBiology(©GarlandSciencefourFigure.MolecularBiologyoftheCell(©GarlandScienceDNAdamagepreventthereplicationofdamagedDNADNA P53:regulatoryprotein(transcriptionregulator)thatrespondstothepresenceofDNAdamage,preventingthecellfromenteringsphaseuntilthedamagehasbeenrepaired.P21:CdkinhibitorFigure.EssentialCellBiology(©GarlandScience9.49.4MMitosisandM-CdkdrivesentryintoMphaseandThecentralproblemforacellinMphaseistoaccuratelysegregateitschromosomes,whichwererepilcatedintheprocedingSphase,sothateachnewdaughtercellreceivesanidenticalcopyofthegenome.Oneofthemostremarkablefeaturesofcell-cyclecontrolisthatasignalproteincomplex,M-Cdk,bringsaboutallofthediverseandintricaterearrangementsthatoccurintheearlystagesofmitosis.M-Cdk:a.triggersthecondensationoftheb.inducestheassemblyofthemitoticForM-Cdktobeactive,itmustbephosphorylatedatonesiteanddephosphorylatedatothersitesFigure.EssentialCellBiology(©GarlandScienceActivatedM-CdkindirectlyactivatesmoreM-Cdk,creatingapositivefeedbackloopOncetheactivationofM-Cdkbegins,thereisanexplosiveincreaseinM-CdkactivitythatdrivesthecellabruptlyfromG2intoMphaseFigure.MolecularBiologyoftheCell(©GarlandScienceCondensins凝缩蛋白helpconfigureduplicatedchromosomesforseparationCondensins：Proteincomplexeswitharing-likestructurethathelpcarryoutchromosomeChromosomecondensation:ProcessbywhichachromosomebecomespackedintoamorecompactstructurepriortoMphaseofthecellcycle.Condensinshelptocoilthemitoticchromatidsintosmaller,morecompactstructuresthatcanbemoreeasilysegregatedduringmitosisCondensedhuman

Thecytoskeletoncarriesoutbothmitosisandmitoticspindle----nucleardivision(mitosis)contractilering----cytoplasmicdivision(cytokinesis)Mitosisand

9.59.5 CentrosomesduplicatetohelpformthetwopolesofthemitoticspindleBeforeMphasebegins,twoeventsmustbe①DNAmustbefully②Inanimalcells,thecentrosomemustbeFigure.EssentialCellBiology(©GarlandSciencecentrosome(cellcenter):centrallylocatedorganelleofanimalcellsthatistheprimarymicrotubule-organizingcenterandseparatestoformthetwospindlepolesduringmitosis.Inthemostanimalcellsitcontainsapairofcentrioles中心粒.aster:star-shapedsystemofmicrotubulesemanatingacentrosomeorformapoleofamitoticcentrosomecycle:dupicationofthecentrosome(duringinterphase)andseparationofthetwonewcentrosomes(atthebeginningofmitosis),toformthepolesofthemitoticspindle.Themitoticspindlestartstoassembleinprophase：firststageofmitosisduringwhichthechromosomesarecondensedbutnotyetattachedtoamitoticspindle.Alsoasuperficiallysimilarstageinmeiosis.

ChromosomesattachtothemitoticspindleatPrometaphase:Stageofmitosisthatprecedesmetaphase.Prometaphasestartsabruptlywiththedisassemblyofthenuclearenvelope,whichbreaksupintosmallmembraneKinetochore动粒：Complexprotein-containingstructureonamitoticchromosometowhichmicrotubulesattach.Thekinetochoreformsonthepartofthechromosomeknownasthecentromere着丝粒.chromatidpairsonthemitoticspindle,suchthatonechromatidisattachedtoonespindlepoleandtheotherchromatidtotheoppositepole.KinetochoresattachchromosomestothemitoticFigure.EssentialCellBiology(©GarlandScienceElectronmicrographofanFigure.MolecularBiologyoftheCell(©GarlandScienceThreeclassesofmicrotubulesmakeupthemitoticspindleinananimalcell Figure.EssentialCellBiology(©GarlandScienceFourmajormotorproteins(yellow)oftheSpindleself-organizationbymotorHowopposingforcesmaydrivechromosomestothemetaphaseFluorescencemicrographofchromsomesatthemetaphaseplateofarealmitoticspindleChromosomesaidintheassemblyofthemitoticnormalspindleformedwithcentrosomesinanormallyAspindleformedwithoutcentrosomesinanembryothatinitiateddevelopmentwithoutfertilizationandthuslacksthecentrosomenormallyprovidedbythespermwhenitfertilizestheegg. Chromosomeslineupatthespindleequatoratmetaphase中期metaphase：Stageofmitosisatwhichchromosomesarefirmlyattachedtothemitoticspindleatitsequatorbuthavenotyetsegregatedtowardoppositea:Thecontinualgrowthandshrinkageofthemicrotubules.b:Theactionofmicrotublemotorproteins.Proteolysistriggerssister-chromatidseparationandthecompletionofmitosisatanaphase后期anaphase后期:stageofmitosisduringwhichthetwosetsofchromosomesseparateandmoveawayfromeachother.ComposedofanaphaseAchromosomesmovetowardthetwospindlepoles)andanaphaseB(spindlepolesmoveapart).Atthebeginningofanaphase后期eachpairofsisterchromatidsseparatesRapidinactivationofM-CdkhelpstoinitiatetheexitfromAnaphasepromotingcomplex(APC):ARapidinactivationofM-CdkhelpstoinitiatetheexitfromFigure.MolecularBiologyoftheCell(©GarlandScienceTheAPCtriggerstheseparationofsisterchromatidsbypromotingthedestructionofcohesins粘连蛋白 Unattachedchromosomesblocksister-chromatidseparationAdivingcellmustensurethateverychromosomeisattachedproperlytothespindlebeforeitcompletesmitosis.Thecellmakesuseofanegativesignal:thecell-cyclecontrolsystem.spindleassemblyThenuclearenvelopere-formsattelophasetelophase：Finalstageofmitosisinwhichthetwosetsofseparatedchromosomesdecondenseandbecomeenclosedbynuclearenvelopes.Thenuclearenvelopesbreakdownandre-formsduringFigure.EssentialCellBiology(©GarlandScienceMphaseisconventionallydividedintosix1.前期2.前中期3.TheeventsofeucaryoticcelldivisionasseenunderamicroscopeFigure.MolecularBiologyoftheCell(©GarlandSciencemitoticspindle--nucleardivision(mitosis)contractilering--cytoplasmicdivision(cytokinesis)cytokinesis:Divisionofthecytoplasmofaplantoranimalcellintotwo,asdistinctfromthedivisionofitsnucleus(whichismitosis)ThemitoticspindledeterminestheplaneofcytoplasmiccleavageThecleavagefurrowifformedbytheactionofthecontractileringunderneaththeplasmamembraneThecontractileringofanimalcellsismadeofactinandmyosin ThecontractileringdividesthecellintwoMitosiswithoutcytokinesisintheDrosophilaFigure.MolecularBiologyoftheCell(©GarlandScienceAnimalcellschangeshapeduringMTheplasmamembraneproteinsresponsibleforattachingthecellstothesubstratum—theintegrins整联蛋白—becomephosphorylatedandthusweakentheirgrip.Cytokinesisinplantcellsinvolvestheformationofanewwall成膜 ThespecialfeaturesofcytokinesisinahigherFigure.MolecularBiologyoftheCell(©GarlandScience Membrane-enclosedorganellesmustbedistributedtodaughtercellswhenacellOrganellessuchasmitochondriaandchloroplastscannotassemblespontaneouslyfromtheirindividualcomponents;theyariseonlyfromthegrowthanddivisionofthepreexisting9.79.7ControlofcellnumberandcellThreefundamentalprocesseslargelyorganandbodycellgrowthcelldeatheachoftheseDependsonprogramsintrinsictotheindividualItisregulatedbysignalsfromotherApoptosishelpsregulateanimalcellprogrammedcelldeath/apoptosis:normal,begintypeofprogrammedcelldeathinwhichacellshrinks,fragmentsitsDNA,andaltersitssurfacesoastoactivatethecell’sphagocytosisbymacrophages.Inadulttissues,celldeathusuallyexactlybalancescellApoptosisinthedevelopingmousepawsculptsthedigitsCelldiewhenthestructuretheyformisnolongerDuringmetamorphosis变态反应,atadpolechangesintoafrogthecellsinitstailareinducedtoundergoapoptosis.ItisstimulatedbyanincreaseinthyroidhormoneintheApoptosisismediatedbyanintracellularproteolyticCellsthatdieasaresultofacuteinjurytypicallyswellandbust,spillingtheircontentsallovertheirneighbors,aprocesscalledcellnecrosis坏死.Thiseruptiontriggersapotentiallydamaginginflammatoryresponse炎症反应.cell apoptosis(inadevelopingThemachinerythatisresponsibleforapoptosisseemstobesimilarinallanimalcellsApoptosisismediatedbyanintracellularproteolyticApoptosisismediatedbyanintracellularproteolyticThedeathprogramisregulatedbytheBcl2familyofintracellularproteinsBcl2family:familyofintracellularproteinsthateitherpromoteorinhibitapoptosisbyregulatingtheactivationofmoteapoptosis--BaxandBak,Inhibitapoptosis--Apoptosome凋亡小体:cytochromecpromotestheassemblyofalarge,seven-armedpinwheel-likestructurethatrecruitsspecificprocaspasemolecules,formingaproteincomplex.ThethreeclassesofFigure.MolecularBiologyoftheCell(©GarlandScienceBaxandBakaredeath-promotingmembersoftheBcl2familyofintracellularproteinsthatcantriggerapoptosisbyreleasingcytochromecfrommitochondrialikestructureFigure.EssentialCellBiology(©GarlandScienceReleaseofcytochromecfromduringapoptosisFigure.MolecularBiologyoftheCell(©GarlandScienceActivatedAktpromotesthecellactivation Figure.EssentialCellBiology(©GarlandScienceAnimalcellsrequireextracellularsignalstosurvive,grow,anddivideunicellularorganisms—tendtogrowanddividefastmulticellularorganisms—growanddividearecontrolledcelltosurvive,

chemicalsignalsfromothercells(neighbors)

a.solubleproteinsteinsboundtothesurfaceofothercellsortheextracellularmatrix

survivalfactorsgrowthfactorsAnimalcellsrequiresurvivalfactorstoavoidcelldeathhelpsadjustthenumberofdevelopingnervecellstothenumberoftargetcellstheycontactsurvivalfactorsusuallyactbybindingtocell-surfaceTheseactivatedreceptorsthenturnonintracellularsignalingpathwaythatkeepthedeathprogramsuppressed,usuallybyregulatingmembersoftheBcl2familyofproteins.increasetheproductionofBcl2,aproteinthatsuppressesapoptosis.ThreewaysthatextracellularsurvivalfactorscaninhibitFigure.MolecularBiologyoftheCell(©GarlandScienceMitogens促有丝分裂因子stimulatecellMostMitogensaresecretedsignalproteinsthatbindtocell-surfacereceptor.mitogens+receptor initiatevariousintracellularsignaling releasethemolecularbakes分子刹车thatblockthetransitionfromG1intoSphase.molecularbakes----retinoblastomaRb)theRbproteinismissingordefectiveMitogens----platelet-derivedgrowthfactororPDGF(alsogrowthfactorsOnewayinwhichmitogensstimulatecellproliferationisbyinhibitingtheRbproteincell-cycleentryandS-phaseinitiationinanimalcellsCell-cyclearrestorapoptosisinducedbyexcessivestimulationofmitogenicpathwaysGrowthfactorsstimulatecellstoRatfibroblastsproliferatinginresponsetogrowthfactorsandExtracellulargrowthfactorsincreasethesynthesisanddecreasethedegradationofAnervecellandaverydifferentinsizeFigure18-46EssentialCellBiology(©GarlandScience Someextracellularsignalproteinsinhibitcellsurvival,division,orgrowthTheeffectoffreshmediumonaconfluentcellFigure.MolecularBiologyoftheCell(©GarlandScienceMutationofthemyostatingene肌肉生成抑制素基因leadstoadramaticincreaseinmusclemassFigure.EssentialCellBiology(©GarlandSciencehaploidhaploid单倍体Acellororganismwithonlyonesetofchromosomes,asinaspermcellorabacterium.9.8Diploid二倍体:Acellororganismcontainingtwosetsofhomologouschromosomesandhencetwocopiesofeachgeneorgeneticlocus.meiosis:specialtypeofcelldivisionbywhichandspermcellsaremade.TwosuccessivenucleardivisionswithonlyoneroundofDNAreplicationgeneratesfourhaploiddaughtercellsfromaninitialdiploidcell. HaploidgermcellsareproducedfromdiploidcellsthroughmeiosisTheultimatereductioninch