CellproliferationanditsregulationSignificance:1.Forthegrowthanddevelopmentofamulticellularorganism,andforthegenerationofoffspring;2.Produceneworganismsinunicellularspecies;3.Renewtheaging,apoptoticcells,anddamagedtissue;So,cellproliferationisoneofthemostimportantcharactersforlifeChapter11迈鼎Cellcyclephases:Interphase:G1-S-G2Mphase:Mitosis,CytokinesisDifferentcellcyclelengthSomeeukaryoticcellcycletimesThegreatestvariationoccursinthedurationofG1Theshortesteukaryoticdivisioncyclesofallaretheearlyembryoniccellcycles,noG1andG2BiochemicaleventsofcellcycleG1phase:Synthesizeproteins(RNA)fortheDNAreplication.Uncondensechromatin.Sphase:SynthesisofDNAandHistonesG2phase:Synthesisofafewproteins(RNA)Mphase:MitosisandmeiosisandcytokinesisTwodaughtercellsChromosomecondenseMitoticspindleContractileringThreecategoriesofcellsinvivo(1)CyclingcellsDividingcontinuously—Stemcells(2)G0cellsDonotdividenormally,butdividewhengivenanappropriatestimulus:livercells,lymphocytes(3)TerminallyDifferentiatedcellsHighlyspecialized,havelosttheabilitytodivideuntiltheydie:musclecells,redbloodcells,nervecellsEmbryocellsCyclingcellsG0cellsTerminalcellsB.Synchronizationofcell(forcellpopulation)(1)NaturalsynchronizationEarlyembryoinmostinvertebratesandafewvertebratesFruitflyembryo(2)SelectedsynchronizationartificiallyIsolationofcellsinMphaseIsolationofcellsbycentrifugation(3)SynchronizationofcellsinducedbydrugsBlockingDNAsynthesisbyTdRG1/S—TdRG1SG2MG1/SBlockingcellsinmetaphasebycolchicineAffecttheassemblyofmitoticspindleSpecialcellcycles—Earlyembryo(30min/cellcycle)(1)NoG1andG2phase,allrepliconsareactivated,soSphaseisveryshort(2)HavelittleornoneedtosynthesizecomponentsotherthanDNA,celldivision(3)NocellgrowthduringcellcycleFrogXenopuslaevis2.Mitosis(1)ProphaseChromatinscondensetoformcompactedmitoticchromosomesActivatedM-Cdkphosphrylatescondensinsubunits,triggeringtheassemblyofcondensincomplexesonDNAandcondensationofthechromosome.ThecondensincanuseenergyofATPhydtolysistopromoteDNAcoiling(invitro).Thesisterchromatidsaregluedtogetherbymultisubunitproteincomplexcalledcohesins.CentrosomeduplicatedatS,andseparatetoformmitoticspindleatthebeginningofprophaseAssemblyofkinetochoreattheendofprophaseGolgi,ERetc.dispersetoformvesicles;kinetochoreassemblySchematicrepresentationofthekinetochore(2)PrometaphaseNuclearenvelopesbreakdown(Laminphosphorylation)SpindleMTscapturechromosomesThepushingandpullingforcesdrivethechromosomestothemetaphaseplate.MTbehaviorduringformationofthemetaphaseplate.Initially,MTfromoppositepolesaredifferentinlength.Experimentaldemonstrationoftheimportanceofmechanicaltensioninmetaphasecheckpointcontrol.(3)MetaphaseAllchromosomesalignatmetaphaseplateMicrotubulesarehighlydynamicinthemetaphasespindle.TheeventsofAnaphase:BothanaphaseAandanaphaseBcontributetothemovementofchromosometowardthespindlepolesAnaphaseA:Themovementofthechromosomestowardthepoles;KinetochoreMTdisaassenbleatbothendsduringanaphaseA.AnaphaseB:Thetwospindlepolesmovefartherapart.BothpushingandpullingforcescontributetoanaphaseB(4)AnaphaseAnaphaseB:Thetwospindlepolesmovefartherapart.TheslidingofoverlapMTatanaphase.MetaphaseLateanaphaseAmodelexplainsthechromosomemovementinanaphaseTwoalternativemodelsofhowthekinetochoremaygenerateapolewardforceonitschromosomeduringanaphaseA.ThecontrolofAnaphase:SCFandAPCactivitiesduringthecellcycleCdc20andcdh1aresubunitstobindingAPC.APCcdc20becomesactivatedatthemetaphase/anaphasetransition.Securin:anaphaseinhibitor.Thedestructionofsecurinbyproteasomesattheendofmetaphasestartsatrainreactionthatleadstothecleavageofthecohesincomplex.Cohesinholdssisterchromatidstogether.Destructionofcohesintriggerstheseparationoftwochromatids.Cohesin细胞周期中SCF与APC的活性。SCF和APC是多亚基复合体,它们将底物蛋白泛素化,致使底物由蛋白酶体降解。(a)SCF主要在间期有活性,而APC主要在有丝分裂期有活性。APC有两种,它们的区别在于分别含Cdc20或Cdh1亚基,亚基改变APC识别的底物。有丝分裂中,APCCdc20比APCCdh1早激活。(b)APCCdc20负责降解抑制后期的蛋白,如securin,它们的降解促使细胞由中期转至后期。APCCdh1负责蛋白泛素化(如M-cyclin),M-cyclin抑制细胞脱离有丝分裂,泛素化底物蛋白的降解促使细胞M-G1期转换。Thespindlecheckpoint(mammaliancellinlateprometaphaselabeledwithanibodiesagainstthespindlecheckpointproteinMad2andtubulin).Mad2Thespindle-attachmentcheckpoint:Anaphaseisdelayeduntilallchromosomsarepositionedatthemetaphaseplate已发现Mad2与Cdc20结合,抑制APC的激活;只有当Mad2分子从所有的染色体上失去后,APC才能被激活,后期才能开始.(5)TelophaseChromosomeuncondenseNuclearenvelopereformsaroundindividualchromosomeGolgi,ERreconstructNucleolusreassembleMitosisends3.Cytokinesis(1)InanimalcellsTheMTofmitoticspindledeterminetheplaneofanimalcelldivision;Mitosiscanoccurwithoutcytokinesis.Contractilering:ActinandmyosinIIinthecontractileringgeneratetheforceforcytokinesis(2)Inplantcells:Thephragmoplastguidescytokinesisinhigherplants;Theassemblyofthecellplatebeginsinlateanaphaseandisguidedbyphragmoplast4.MeiosisThecomparisonofm