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BIOL221
Ch12CellCycleandMitosis
TheKeyRolesofCellDivision
• Celldivision
• Cellularreproduction
• Anabilityoforganismsthatbestdistinguisheslivingthingsfromnonlivingmatter
• Unicellularorganisms
• Cellulardivisionreproducestheentireorganism
• Multicellularorganisms
• dependoncelldivisionfor:
• Developmentfromafertilizedcell
• Growth
• Repair
• Cellcycle
• Lifeofacellfromformationtoitsowndivision
• Celldivisionisanintegralpart
CellDivision
100 µm 200 µm 20 µm
(a) Reproduction (b) Growth anddevelopment
(c) Tissue renewal
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CellularOrganizationoftheGeneticMaterial• Genome
• AlltheDNAinacell
• MaybeasingleDNAmolecule
• prokaryoticcells
or…
• ManyDNAmolecules
• eukaryoticcells
• Chromosomes
• PackagedDNAmoleculesinacell
• OnemoleculeofDNAequalsonechromosome
• Humanrange51million- 245millionbasepairsperchromosome
• Eacheukaryoticspecies
• Hasacharacteristicnumberofchromosomesineachcellnucleus
• Somaticcells
• Non-reproductivecells
• havetwoofeachtypeofchromosome
• Diploid- 46
• Germcells
• MakeGametes
• Reproductivecells:spermandeggs
• Onlyoneofeachchromosome
• Haploid- 23
CellularOrganizationoftheGeneticMaterial
• Chromatin
• ComplexofDNAandproteinthatcondensesduringcelldivision
• InEukaryoticchromosomes
• TypicalDNAformwhennotactivelydividing
CellularOrganizationoftheGeneticMaterial
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ChromosomeDistributionDuringEukaryoticCellDivision• Preparationforcelldivision
• DNAisreplicatedandthe
chromosomescondense
• Sisterchromatids
• Duplicatedchromosome
• Twocopieswhichseparate
duringcelldivision
• Centromere
• Junctionpointoftheduplicated
chromosome,wherethetwo
chromatidsareattached
Fig.12-4
0.5 µm Chromosomes
Chromosomeduplication(including DNAsynthesis)
Chromo-some arm
Centromere
Sisterchromatids
DNA molecules
Separation ofsister chromatids
Centromere
Sister chromatids
• Eukaryoticcelldivisionconsistsof:
• Mitosis
• Divisionoftheduplicatedgenome
• Cytokinesis
• Divisionofthecytoplasm
• Meiosis
• Avariationofcelldivisionformakinggametes
• Yieldsnon-identicaldaughtercells
• Onlyonesetofchromosomes,halfasmanyastheparentcell
• Haploid
TypesofEukaryoticCellDivision
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PhasesoftheCellCycle
• Thecellcycleconsistsof2phases
• Mitotic(M)phase
• mitosisandcytokinesis
• Interphase
• cellgrowth
• copyingofchromosomesin
preparationforcelldivision
• Interphase
• about90%ofthecellcycle
• canbedividedintosubphases:
• G1 phase
• firstgap
• Sphase
• Synthesisofduplicate
DNA
• G2 phase
• secondgap
PhasesoftheCellCycle- Interphase
S(DNA synthesis)G1
G2
• Mitosisisconventionallydividedintofive
phases:
• Prophase
• Prometaphase
• Metaphase
• Anaphase
• Telophase
• Cytokinesisiswellunderwaybylate
telophase
PhasesoftheCellCycle- MitoticPhase
PLAY
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Fig.12-6
G2 of Interphase
Centrosomes(with centriolepairs)
Chromatin(duplicated)
Nucleolus Nuclearenvelope
Plasmamembrane
Early mitoticspindle
Aster Centromere
Chromosome, consistingof two sister chromatids
Prophase Prometaphase
Fragmentsof nuclearenvelope
Nonkinetochoremicrotubules
Kinetochore Kinetochoremicrotubule
Metaphase
Metaphaseplate
Spindle Centrosome atone spindle pole
Anaphase
Daughterchromosomes
Telophase and Cytokinesis
Cleavagefurrow
Nucleolusforming
Nuclearenvelopeforming
Prophase PrometaphaseG2 of Interphase
PrometaphaseProphaseG2 of InterphaseNonkinetochore
microtubulesFragmentsof nuclearenvelope
Aster CentromereEarly mitoticspindle
Chromatin(duplicated)
Centrosomes(with centriolepairs)
Nucleolus Nuclearenvelope
Plasmamembrane
Chromosome, consistingof two sister chromatids
Kinetochore Kinetochoremicrotubule
• Interphase(G2)
• Diffusechromatin
• duplicatedstate
• Chromosomesnotvisible
underlightmicroscope
• Nucleolusstillpresent
Prophase PrometaphaseG2 of Interphase
PrometaphaseProphaseG2 of InterphaseNonkinetochore
microtubulesFragmentsof nuclearenvelope
Aster CentromereEarly mitoticspindle
Chromatin(duplicated)
Centrosomes(with centriolepairs)
Nucleolus Nuclearenvelope
Plasmamembrane
Chromosome, consistingof two sister chromatids
Kinetochore Kinetochoremicrotubule
• Prophase
• Chromatinbegins
tocondense
• Centrosomes
begintomigrate
• Spindlebeginsto
grow
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Prophase PrometaphaseG2 of Interphase
PrometaphaseProphaseG2 of InterphaseNonkinetochore
microtubulesFragmentsof nuclearenvelope
Aster CentromereEarly mitoticspindle
Chromatin(duplicated)
Centrosomes(with centriolepairs)
Nucleolus Nuclearenvelope
Plasmamembrane
Chromosome, consistingof two sister chromatids
Kinetochore Kinetochoremicrotubule
• Prometaphase
• Chromsomes fullycondensed
• Nuclearmembranebrokendown
• Centrosomesestablishpoles
• Spindlefibersattachtokinetochores
Fig.12-6c
Metaphase Anaphase Telophase and Cytokinesis
Metaphase Anaphase Telophase and Cytokinesis
Cleavagefurrow
Nucleolusforming
Metaphaseplate
Centrosome atone spindle pole
SpindleDaughterchromosomes
Nuclearenvelopeforming
• Metaphase
• Chromosomesline
upatmetaphase
plate
• Singlefile
• Guidedby
spindlefibers
Fig.12-6c
Metaphase Anaphase Telophase and Cytokinesis
Metaphase Anaphase Telophase and Cytokinesis
Cleavagefurrow
Nucleolusforming
Metaphaseplate
Centrosome atone spindle pole
SpindleDaughterchromosomes
Nuclearenvelopeforming
• Anaphase
• Sisterchromatids
separate
• Now
daughter
chromosomes
• Migratetopoles
• Spindlefibers
shorten
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Fig.12-6c
Metaphase Anaphase Telophase and Cytokinesis
Metaphase Anaphase Telophase and Cytokinesis
Cleavagefurrow
Nucleolusforming
Metaphaseplate
Centrosome atone spindle pole
SpindleDaughterchromosomes
Nuclearenvelopeforming
• Telophase
• Daughter
chromosomes
reachpoles
• Beginto
decondense
• Nuclear
membranesform
• Cytokinesis begins
• Cleavagefurrow
forms
TheMitoticSpindle:ACloserLook
• Mitoticspindle
• Apparatusofmicrotubulesthatcontrolschromosomemovementduringmitosis
• Centrosome
• Microtubuleorganizingcenter
• Consistsoftwocentrioles
• Duringprophaseassemblesspindlemicrotubules
• Thecentrosomereplicates
• formingtwocentrosomes
• migratetooppositeendsofthecell
• spindlemicrotubulesgrowoutfromthem
• Aster
• aradialarrayofshortmicrotubules
• extendsfromeachcentrosome
• anchorscentrosometorestofcytoskeleton
• Thespindleincludesthecentrosomes,thespindlemicrotubules,andtheasters
TheMitoticSpindle:ACloserLook
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• Kinetochore
• Attachmentpointfor
microtubulesofspindle
• Proteinstructurebound
toDNAatcentromere
TheMitoticSpindle
Fig.12-7
Microtubules Chromosomes
Sisterchromatids
Aster
Metaphaseplate
Centrosome
Kineto-chores
Kinetochoremicrotubules
Overlappingnonkinetochoremicrotubules
Centrosome 1 µm
0.5 µm
• Inanaphase
• sisterchromatidsseparateandmovealongthekinetochore
microtubulestowardoppositeendsofthecell
• Spindlemicrotubules
• shortenbydepolymerizingattheirkinetochoreends
TheMitoticSpindle
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Fig.12-8
EXPERIMENT
Kinetochore
RESULTS
CONCLUSION
Spindlepole
Mark
Chromosomemovement
Kinetochore
Microtubule Motorprotein
Chromosome
Tubulinsubunits
• Non-kinetochoremicrotubules
• fromoppositepolesoverlapandpushagainsteachotherelongatingthe
cell
• Intelophase
• geneticallyidenticaldaughternucleiformatoppositeendsofthecell
TheMitoticSpindle
Cytokinesis:ACloserLook• Animalcells
• cytokinesisoccursbycleavage,formingacleavagefurrow
• Plantcells
• acellplateformsduringcytokinesis
Cleavage furrow100 µm
Contractile ring ofmicrofilaments
Daughter cells
(a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM)
Vesiclesformingcell plate
Wall ofparent cell
Cell plate
Daughter cells
New cell wall
1 µm
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Sea Urchin (Time Lapse)
Animal Mitosis
PLAY
PLAY
BinaryFission
• Prokaryotes(Eubacteriaandarchaebacteria)
• Reproducebyatypeofcelldivisioncalledbinaryfission
• Singlechromosomereplicates(beginningattheoriginof
replication)
• twodaughterchromosomesactivelymoveapart
Fig.12-11-1
Origin ofreplication
Two copiesof origin
E. coli cell Bacterialchromosome
Plasmamembrane
Cell wall
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Fig.12-11-2
Origin ofreplication
Two copiesof origin
E. coli cell Bacterialchromosome
Plasmamembrane
Cell wall
Origin Origin
Fig.12-11-3
Origin ofreplication
Two copiesof origin
E. coli cell Bacterialchromosome
Plasmamembrane
Cell wall
Origin Origin
Fig.12-11-4
Origin ofreplication
Two copiesof origin
E. coli cell Bacterialchromosome
Plasmamembrane
Cell wall
Origin Origin
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TheEvolutionofMitosis
• Binaryfissionpredatesmitosis
• Sinceprokaryotesevolvedbeforeeukaryotes,mitosisprobablyevolved
frombinaryfission
• Someprotists areintermediatebetweenbinaryfissionandmitosis
• Dinoflagellates
• Diatoms/Yeasts
Bacterialchromosome
Chromosomes
Microtubules
(a) Bacteria
(b) Dinoflagellates
Intact nuclearenvelope
Kinetochoremicrotubule
(c) Diatoms and yeasts
Kinetochoremicrotubule
(d) Most eukaryotesFragments of nuclear envelope
Intact nuclearenvelope
RegulationoftheCellCycle
• Thefrequencyofcelldivisionvarieswiththe
typeofcell
• Musclecells
• Neurons
• Hepatocytes
• Thesecellcycledifferencesresultfrom
regulationatthemolecularlevel
• Signalingmolecules
TheCellCycleControlSystem
• Cellcyclecontrolsystem
• Regulatedbybothinternalandexternalcontrols
• Hasspecificcheckpointswherethecellcyclestopsuntilago-ahead
signalisreceived
SG1
M checkpoint
G2M
Controlsystem
G1 checkpoint
G2 checkpoint
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• G1 checkpoint
• Appearsmostimportant
• cellreceivesago-aheadsignalattheG1 checkpoint,itwillusuallycompletetheS,G2,andMphasesanddivide
• Nogo-aheadsignal
• Cellsexitscycle,switchingintoG0 phase- anon-dividingstate
TheCellCycleControlSystem
G1
G0
G1 checkpoint
(a) Cell receives a go-aheadsignal
G1
(b) Cell does not receive ago-ahead signal
Cyclins&Cyclin-DependentKinases• Twotypesofregulatoryproteins
involvedincellcyclecontrol
• Cyclins
• Cyclin-dependentkinases
(Cdks)
• Activityfluctuatesduring
thecellcycle
• MPF (maturation-promotingfactor)
• Cyclin-Cdkcomplexthat
triggersacell’spassagepasttheG2 checkpointintotheM
phase
Stop/GoSigns:SignalsattheCheckpoints• Internalsignal
• Mcheckpoint
• kinetochoresnotattachedtospindlemicrotubules
• sendamolecularsignalthatdelaysanaphase
• Externalsignals
• Growthfactors
• proteinsreleasedbycertaincellsthatstimulateothercellstodivide
• platelet-derivedgrowthfactor(PDGF)stimulatesthedivisionof
humanfibroblastcellsinculture
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• Otherexternalsignals
• density-dependentinhibition
• crowdedcellsstopdividing
• anchoragedependence
• Mostanimalcellsmustbeattachedtoasubstratuminordertodivide
Stop/GoSigns:SignalsattheCheckpoints
Anchorage dependence
Density-dependent inhibition
Density-dependent inhibition
(a) Normal mammalian cells (b) Cancer cells25 µm25 µm
Tumor
A tumor growsfrom a singlecancer cell.
Glandulartissue
LymphvesselBloodvessel
Metastatictumor
Cancercell
Cancer cellsinvade neigh-boring tissue.
Cancer cells spreadto other parts ofthe body.
Cancer cells maysurvive andestablish a newtumor in anotherpart of the body.
1 2 3 4
• Transformation
• Anormalcellisconvertedtoacancerouscellwhichformstumors
• massesofabnormalcellswithinotherwisenormaltissue
• Benigntumor
• Abnormalcellsremainattheoriginalsite
• Malignanttumors
• Invadesurroundingtissues
• Canmetastasizeexportingcancercellstootherpartsofthebody,possiblyformsecondarytumors
LossofCellCycleControlsinCancerCells
Youshouldnowbeableto:
1. Describethestructuralorganizationoftheprokaryoticgenomeandtheeukaryoticgenome
2. Listthephasesofthecellcycle;describethesequenceofeventsduringeachphase
3. Listthephasesofmitosisanddescribetheeventscharacteristicofeachphase
4. Drawordescribethemitoticspindle,includingcentrosomes,kinetochoremicrotubules,nonkinetochore microtubules,andasters
5. Comparecytokinesisinanimalsandplants
6. Describetheprocessofbinaryfissioninbacteriaandexplainhoweukaryoticmitosismayhaveevolvedfrombinaryfission
7. Explainhowtheabnormalcelldivisionofcancerouscellsescapesnormalcellcyclecontrols
8. Distinguishbetweenbenign,malignant,andmetastatictumors