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CHAPTER 17

171

CYTOSKELETON
2009 Garland Science Publishing

IdentifythecytoskeletalstructuresdepictedintheepithelialcellsshowninFigure
Q171.

FigureQ171
172

Whichofthefollowingstatementsaboutthecytoskeletonisfalse?
(a)
Thecytoskeletonismadeupofthreetypesofproteinfilament.
(b)
ThebacterialcytoskeletonisimportantforcelldivisionandDNA
segregation.
(c)
Proteinmonomersthatareheldtogetherwithcovalentbondsform
cytoskeletalfilaments.
(d)
Thecytoskeletonofacellcanchangeinresponsetotheenvironment.

173

Indicatewhichofthethreemajorclassesofcytoskeletalelementseachstatement
belowrefersto.
A.
monomerthatbindsATP
B.
includeskeratinandneurofilaments
C.
importantforformationofthecontractileringduringcytokinesis
D.
supportsandstrengthensthenuclearenvelope
E.
theirstabilityinvolvesaGTPcap
F.
usedintheeucaryoticflagellum
G.
acomponentofthemitoticspindle
H.
canbeconnectedthroughdesmosomes
I.
directlyinvolvedinmusclecontraction
J.
abundantinfilopodia

174

Whichofthefollowingstatementsaboutthecytoskeletonistrue?
(a)
Alleucaryoticcellshaveactin,microtubules,andintermediatefilaments
intheircytoplasm.

(b)
(c)
(d)
175

Thecytoskeletonprovidesarigidandunchangeablestructureimportant
fortheshapeofthecell.
Thethreecytoskeletalfilamentsperformdistincttasksinthecellandact
completelyindependentlyofoneanother.
Actinfilamentsandmicrotubuleshaveaninherentpolarity,withaplus
endthatgrowsmorequicklythantheminusend.

Rankthefollowingcytoskeletalfilamentsfromsmallesttolargestindiameter(1
=smallestindiameter,4=largest)
______intermediatefilaments
______microtubules
______actinfilament
______myofibril

Intermediate Filaments
176

Whichofthestatementsbelowaboutintermediatefilamentsisfalse?
(a)
Theycanstayintactincellstreatedwithconcentratedsaltsolutions.
(b)
Theycanbefoundinthecytoplasmandthenucleus.
(c)
Theycanbeanchoredtotheplasmamembraneatcellcelljunction.
(d)
Eachfilamentisabout10mindiameter.

177

Intermediatefilamentsaremadefromelongatedfibrousproteinsthatare
assembledintoaropelikestructure.FigureQ177showsthestructureofan
intermediatefilamentsubunit.Youareinterestedinhowintermediatefilaments
areformed,andyoucreateanintermediatefilamentsubunitwhosehelical
regionistwiceaslongasthatofanormalintermediatefilamentbyduplicatingthe
normalhelicalregionwhilekeepingaglobularheadattheNterminusanda
globulartailattheCterminus;youcallthissubunitIFd.Ifyouweretoassemble
intermediatefilamentsusingIF2dasthesubunit,whichofthefollowing
predictionsbelowdescribesthemostlikelyoutcome?

FigureQ177
(a)
(b)
(c)

FilamentsassembledusingIFdwillinteractwithdifferentcytoskeletal
components.
FilamentsassembledusingIFdwillformdimersthataretwiceaslongas
dimersassembledfromnormalintermediatefilaments.
SixteentetramersassembledfromIFdwillbeneededforaropelike
structuretoform.

(d)
178

DimersofIFdwillformbyinteractionswiththeNterminalglobular
headandtheCterminalglobulartail.

Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;useeachword
orphraseonlyonce.
Intermediatefilamentsarefoundmainlyincellsthataresubjectto
mechanicalstress.Mutationsingenesthatdisruptintermediate
filamentscausesomerarehumandiseases.Forexample,theskin
ofpeoplewithepidermolysisbullosasimplexisverysusceptibleto
mechanicalinjury;peoplewiththisdisorderhavemutationsin
their__________________genes,theintermediatefilamentfound
inepithelialcells.Thesefilamentsareusuallyconnectedfromcell
tocellthroughjunctionscalled__________________s.Themain
filamentsfoundinmusclecellsbelongtothe
__________________family;peoplewithdisruptionsinthese
intermediatefilamentscanhavemusculardystrophy.Inthe
nervoussystem,__________________shelpstrengthenthe
extremelylongextensionsoftenpresentinnervecellaxons;
disruptionsintheseintermediatefilamentscanleadto
neurodegeneration.Peoplewhocarrymutationsinthegenefor
__________________,animportantproteinforcrosslinking
intermediatefilaments,haveadiseasethatcombinessymptomsof
epidermolysisbullosasimplex,musculardystrophy,and
neurodegeneration.
desmosome
keratin
kinase

179

lamin
neurofilament
plectin

synapse
vimentin

Matchthetypeofintermediatefilamentwithitsappropriatelocation.
lamins_________
A.nervecells
neurofilaments_________ B.epithelia
vimentins_________
C.nucleus
keratins_________
D.connectivetissue

1710 Keratins,neurofilaments,andvimentinsareallcategoriesofintermediate
filaments.Whichofthefollowingpropertiesbelowisnottrueofthesetypesof
intermediatefilaments?
(a)
Theystrengthencellsagainstmechanicalstress.
(b)
Dimersassociatebynoncovalentbondingtoformatetramer.
(c)
Theyarefoundinthecytoplasm.
(d)
Phosphorylationcausesdisassemblyduringeverymitoticcycle.

1711 Phosphorylationofnuclearlaminsregulatestheirassemblyanddisassembly
duringmitosis.Youaddadrugtocellsundergoingmitosisthatinhibitsthe
activityofanenzymethatdephosphorylatesnuclearlamins.Whatdoyoupredict
willhappentothesecells?Why?
1712 Youareinterestedinunderstandingtheregulationofnuclearlaminaassembly.To
createaninvitrosystemforstudyingthisprocessyoustartwithpartlypurified
nuclearlaminasubunitstowhichyouwilladdbackpurifiedcellularcomponents
todrivenuclearlaminaassembly.Beforeyoustartdoingexperiments,your
instructorsuggeststhatyouconsiderwhattypeofconditionswouldbemost
amenabletotheassemblyofnuclearlaminafromitsindividualsubunitsinvitro.
Whichofthefollowingconditionsdoyoupredictwouldbemostlikelyto
enhancetheassemblyofthenuclearlamina?
(a)
additionofphosphataseinhibitors
(b)
additionofATP
(c)
additionofaconcentratedsaltsolutionthatis10timestheconcentration
normallyfoundinthenucleoplasm
(d)
additionofproteinkinaseinhibitors

Microtubules
1713 Placethefollowinginorderofsize,fromthesmallesttothelargest.
A.
protofilament
B.
microtubule
C.
tubulin
D.
tubulindimer
E.
mitoticspindle
1714 InthethreecelloutlinesinFigureQ1714,indicatethearrangementofthe
microtubules,showingclearlytheirfreeandattachedends.Oneachfigure
indicatetheplusendandtheminusendforoneofthemicrotubules.

FigureQ1714
1715 Whichofthefollowingstatementsaboutmicrotubulesistrue?
(a)
Motorproteinsmoveinadirectionalfashionalongmicrotubulesbyusing
theinherentstructuralpolarityofaprotofilament.
(b)
Thecentromerenucleatesthemicrotubulesofthemitoticspindle.
(c)
Becausemicrotubulesaresubjecttodynamicinstability,theyareused
onlyfortransientstructuresinacell.
(d)
ATPhydrolysisbyatubulinheterodimerisimportantforcontrollingthe
growthofamicrotubule.
1716 Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;useeachword
orphraseonlyonce.
Microtubulesareformedfromthetubulinheterodimer,whichis
composedofthenucleotidebinding__________________protein
andthe__________________protein.Tubulindimersarestacked
togetherintoprotofilaments;__________________parallel
protofilamentsformthetubelikestructureofamicrotubule.
__________________ringsareimportantformicrotubule
nucleationandarefoundinthe__________________,whichis
usuallyfoundnearthecellsnucleusincellsthatarenot
undergoingmitosis.Amicrotubulethatisquicklygrowingwill
havea__________________capthathelpspreventthelossof
subunitsfromitsgrowingend.Stablemicrotubulesareusedin
ciliaandflagella;thesemicrotubulesarenucleatedfroma
__________________andinvolvea__________________plus
twoarrayofmicrotubules.Themotorprotein
__________________generatesthebendingmotionincilia;the
lackofthisproteincancauseKartagenerssyndromeinhumans.
basalbody
myosin
dynein
GTP
twentyone
tubulin

tubulin
UTP
thirteen
centrosome
tubulin
kinesin

ATP
nine
tubulin
four
vimentin
two

1717 ThehydrolysisofGTPtoGDPcarriedoutbytubulinmolecules
________________.
(a)
providestheenergyneededfortubulintopolymerize
(b)
occursbecausethepooloffreeGDPhasrunout
(c)
tipsthebalanceinfavorofmicrotubuleassembly
(d)
allowsthebehaviorofmicrotubulescalleddynamicinstability
1718 Themicrotubulesinacellformastructuralframeworkthatcanhaveallthe
followingfunctionsexceptwhichofthefollowing?
(a)
holdinginternalorganellessuchastheGolgiapparatusinparticular
positionsinthecell
(b)
creatinglongthincytoplasmicextensionsthatprotrudefromonesideof
thecell
(c)
strengtheningtheplasmamembrane
(d)
movingmaterialsfromoneplacetoanotherinsideacell
1719 Youarecuriousaboutthedynamicinstabilityofmicrotubulesanddecidetojoina
labthatworksonmicrotubulepolymerization.Thepeopleinthelabhelpyou
growsomemicrotubulesincultureusingconditionsthatallowyoutowatch
individualmicrotubulesunderamicroscope.Youcanseethemicrotubules
growingandshrinking,asyouexpect.Theprofessorwhorunsthelabgetsina
newpieceofequipment,averyfinelaserbeamthatcanbeusedtosever
microtubules.Sheisveryexcitedandwantstosevergrowingmicrotubulesat
theirmiddle,usingthelaserbeam.
A.
Doyoupredictthatthenewlyexposedmicrotubuleplusendswillgrowor
shrink?Explainyouranswer.
B.
Whatdoyouexpectwouldhappentothenewlyexposedplusendsifyou
weretogrowthemicrotubulesinthepresenceofananalogofGTPthat
cannotbehydrolyzed,andyouthenseveredthemicrotubulesinthe
middlewithalaserbeam?
1720 Whichofthefollowingstatementsregardingdynamicinstabilityisfalse?
(a)
Eachmicrotubulefilamentgrowsandshrinksindependentlyofits
neighbors.
(b)
TheGTPcaphelpsprotectagrowingmicrotubulefromdepolymerization.
(c)
GTPhydrolysisbythetubulindimerpromotesmicrotubuleshrinking.
(d)
Thenewlyfreedtubulindimersfromashrinkingmicrotubulecanbe
immediatelycapturedbygrowingmicrotubulesandaddedtotheirplus
end.
1721 Whichofthesituationsbelowwillenhancemicrotubuleshrinkage?
(a)
additionofadrugthatinhibitsGTPexchangeonfreetubulindimers
(b)
additionofadrugthatinhibitsGTPhydrolysisoftubulindimers

(c)
(d)

additionofadrugthatincreasestheaffinityoftubulinmoleculescarrying
GDPforothertubulinmolecules
additionofadrugthatblockstheabilityofatubulindimertobindto
tubulin

1722 ThegraphinFigureQ1722showsthetimecourseofthepolymerizationofpure
tubulininvitro.Youcanassumethatthestartingconcentrationoffreetubulinis
muchhigherthanitisincells.

FigureQ1722
A.
B.

Explainthereasonfortheinitiallagintherateofmicrotubuleformation.
WhydoesthecurveleveloutafterpointC?

1723 Whichofthefollowingstatementsaboutorganellarmovementinthecellisfalse?
(a)
Organellesundergosaltatorymovementinthecell.
(b)
Onlythemicrotubulecytoskeletonisinvolvedinorganellarmovement.
(c)
MotorproteinsinvolvedinorganellarmovementuseATPhydrolysisfor
energy.
(d)
Organellesareattachedtothetaildomainofmotorproteins.
1724 Microtubulesareimportantfortransportingcargoinnervecellaxons,as
diagrammedinFigureQ1724.Noticethatthetwotypesofcargoaretravelingin
oppositedirections.Whichofthefollowingstatementsislikelytobefalse?

FigureQ1724
(a)
(b)
(c)
(d)

Thegraycargoisattachedtodynein.
TheblackcargoandthegraycargorequireATPhydrolysisfortheir
motion.
Theblackcargomovingtowardtheaxonterminalcontainsadomainthat
specificallyinteractswiththetaildomainofaparticularkindofmotor.
Theblackcargoandthegraycargoaremovingalongmicrotubulesof
oppositepolarity.

1725 Doyouagreeordisagreewiththisstatement?Explainyouranswer.
Minusenddirectedmicrotubulemotors(likedyneins)delivertheir
cargototheperipheryofthecell,whereasplusenddirected
microtubulemotors(likekinesins)delivertheircargotothe
interiorofthecell.
1726 Whichofthefollowingstatementsiscorrect?
Kinesinsanddyneins____________________.
(a)
havetailsthatbindtothefilaments
(b)
movealongbothmicrotubulesandactinfilaments
(c)
oftenmoveinoppositedirectionstoeachother
(d)
derivetheirenergyfromGTPhydrolysis
1727 MatchthefollowinglabelstothenumberedlinesonFigureQ1727.

FigureQ1727
A.
B.
C.
D.

minusendofmicrotubule
tailofmotorprotein
cargoofmotorprotein
headofmotorprotein

WhichofthetwomotorsinFigureQ1727ismostprobablyakinesin?Explain
youranswer.
1728 Somelowervertebratessuchasfishandamphibianscancontroltheircolorby
regulatingspecializedpigmentcellscalledmelanophores.Thesecellscontain
small,pigmentedorganelles,termedmelanosomes,thatcanbedispersed
throughoutthecell,makingthecelldarker,oraggregatedinthecenterofthecell
tomakethecelllighter.Youpurifythemelanosomesfrommelanophoresthat
haveeitheraggregatedordispersedmelanosomesandfindthat:
1.
aggregatedmelanosomescopurifywithdynein;
2.
dispersedmelanosomescopurifywithkinesin.
Giventhissetofdata,proposeamechanismforhowtheaggregationanddispersal
ofmelanosomesoccur.
1729 Indicatewhethereachofthefollowingstatementsreferstoaciliarymicrotubule,
amicrotubuleofthemitoticspindle,bothtypesofmicrotubule,orneithertypeof
microtubule.
A.
Thebasalbodyistheorganizingcenter.
B.
Themonomerissequesteredbyprofilin.
C.
Itisarrangedina9+2array.
D.
Itisnucleatedatthecentrosome.
E.
Itusesdyneinmotors.
F.
Itisinvolvedinspermmotility.
G.
Itisinvolvedinmovingfluidoverthesurfaceofcells.
1730 Whichofthefollowingitemsbelowarenotimportantforflagellarmovement?
(a)
sarcoplasmicreticulum
(b)
ATP
(c)
dynein
(d)
microtubules
1731 FigureQ1731Ashowshowthemovementofdyneincausestheflagellumto
bend.Ifinsteadofthenormalsituation,thepolarityoftheadjacentdoubletof
microtubulesweretobereversed(seeFigureQ1731B)whatdoyoupredict
wouldhappen?

FigureQ1731
(a)
(b)
(c)
(d)

Nobendingwouldoccur.
BendingwouldoccurexactlyasdiagrammedinFigureQ1731A.
Bendingwouldoccur,exceptthattherightmicrotubuledoubletwould
movedownrelativetotheleftone.
Thetwomicrotubuledoubletswouldslideawayfromeachother.

1732 FigureQ1732showstwoisolatedouterdoubletmicrotubulesfromaeucaryotic
flagellumwiththeirassociateddyneinmolecules.

FigureQ1732
A.
B.
C.

SketchwhatwillhappentothisstructureifitissuppliedwithATP.
Sketchwhatwillhappentothisstructureifthelinkingproteinsare
removedanditissuppliedwithATP.
Inacompleteflagellum,whatwouldhappenifallthedyneinmolecules
wereactiveatthesametime?

Actin Filaments
1733 Whichofthefollowingstatementsaboutactinisfalse?
(a)
ATPhydrolysisdecreasesactinfilamentstability.
(b)
Actinatthecellcortexhelpsgoverntheshapeoftheplasmamembrane.

(c)
(d)

Actinfilamentsarenucleatedatthesideofexistingactinfilamentsin
lamellipodia.
Thedynamicinstabilityofactinfilamentsisimportantforcellmovement.

1734 Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;useeachword
orphraseonlyonce.
Therearemanyactinbindingproteinsincellsthatcanbindto
actinandmodifyitsactivity.Someproteinssuchas
__________________bindtoactinmonomers,sequesteringthem
untilneededforfilamentformation.__________________
proteinsbindtotheendofactinfilaments.The
__________________proteinsareimportantfornucleationofthe
branchedactinstructurescommonlyfoundinthe
__________________ofmovingcells,whereas
__________________proteinsareimportantfortheformationof
unbranchedactinfilamentscommonlyfoundin
__________________.Proteinsbelongingtothe
__________________familyofGTPasesregulatechangesinthe
actincytoskeletoninresponsetoextracellularsignals.
capping
integrin
filopodia
Rho
severing

lamellipodia
ARP
bundling
gelsolin
cytochalasin

thymosin
formin
GAP
contracting
lamin

1735 Doyouagreeordisagreewiththefollowingstatement?Explainyouranswer.
Nucleotidehydrolysishasasimilarroleinactinpolymerizationandintubulin
polymerization.
1736 Actinbindingproteinsbindtoactinandcanmodifyitsproperties.Youpurifya
protein,Cap1,thatseemstobindandcaponeendofanactinfilament,although
youdonotknowwhetheritbindstheplusendortheminusend.Todetermine
whichendoftheactinfilamentyourproteinbindsto,youdecidetoexaminethe
effectofCap1onactinpolymerizationbymeasuringthekineticsofactinfilament
formationinthepresenceandtheabsenceofCap1protein.Youobtainthe
followingresults(seeFigureQ1736).DoyouthinkCap1bindstheplusendor
theminusend
ofactin?
Explainyour
reasoning.

FigureQ1736
1737 Inthecell,theconcentrationofactinmonomerishigherthantheconcentration
requiredforpurifiedactinmonomerstopolymerizeinvitro.Thymosinisa
proteinthatcanbindactinmonomers.Ifyouweretoaddadrugthatinhibitsthe
abilityofthymosintobindactinmonomers,whateffectwouldthishaveonactin
polymerization?Explainyouranswer.
1738 Whichofthefollowingstatementsisfalse?
(a)
Cytochalasinspreventactinpolymerization.
(b)
Actinfilamentsareusuallyexcludedfromthecellcortex.
(c)
Integrinsaretransmembraneproteinsthatcanbindtotheextracellular
matrix.
(d)
ARPscanpromotetheformationofbranchedactinfilaments.
1739 Cellmovementinvolvesthecoordinationofmanyeventsinthecell.Whichofthe
followingphenomenaarenotrequiredforcellmotility?
(a)
Myosinmediatedcontractionattherearofthemovingcell.
(b)
Integrinassociationwiththeextracellularenvironment.
(c)
Nucleationofnewactinfilaments.
(d)
ReleaseofCa2+fromthesarcoplasmicreticulum.
1740 Thefollowingproteinsareimportantforcellmovement.Matchthefollowing
proteinswiththeirfunction.
myosinII_________
A.nucleationofnewactinfilaments
ARPproteins_________ B.regulationoftheavailabilityofactinmonomers
profilin_________
C.involvementinfocalcontacts
integrins_________
D.contractingtherearofthecell
1741 FigureQ1741
alamellipodium.
statementsisfalse?

showstheleadingedgeof
Whichofthefollowing

FigureQ1741
(a)
(b)
(c)
(d)

Nucleationofnewfilamentsnearattheleadingedgepushestheplasma
membraneforward.
ARPproteinsnucleatethebranchedactinfilamentsinthelamellipodia.
Cappingproteinsbindtotheminusendofactinfilaments.
ThereismoreATPboundactinattheleadingedgethanintheactin
filamentsawayfromtheleadingedge.

1742 YouareexaminingacelllineinwhichactivationoftheRhofamilymemberRac
promoteslamellipodiaformation.Whichofthefollowingstatementsismost
likelytobetrue?
(a)
CellscarryingaRacmutationthatmakesRacactasifitisalwaysbound
toGTPwillpolymerizemoreunbranchedactinfilamentsthannormal
cells.
(b)
CellscarryingaRacmutationthatmakesRacunabletoexchangeGDPfor
GTPwillpolymerizemoreunbranchedactinfilamentsthannormalcells.
(c)
CellscarryingaRacmutationthatmakesRacactasifitisalwaysbound
toGTPwillpolymerizemorebranchedactinfilamentsthannormalcells.
(d)
CellscarryingaRacmutationthatmakesRacunabletoexchangeGDPfor
GTPwillpolymerizemorebranchedactinfilamentsthannormalcells.
1743 Inthebuddingyeast,activationoftheGTPbindingproteinCdc42occurson
bindingofanexternalsignal(pheromone)toaGproteinlinkedreceptor.
ActivationofCdc42promotesactinpolymerization.Predictwouldhappento
actinpolymerization,incomparisonwithpheromonetreatedcells,inthe
followingcases.
A.
YouaddpheromonetoaninhibitorofGproteinlinkedreceptors.
B.
YouaddpheromonetoanonhydrolyzableanalogueofGTP.
1744 Yourfriendworksinabiotechcompanythathasjustdiscoveredadrugthat
seemstopromotelamellipodiaformationincells.Whichofthefollowing
moleculesbelowisunlikelytobeinvolvedinthepathwaythatthisdrugaffects?

(a)
(b)
(c)
(d)

Rac
ARP
actin
myosin

Muscle Contraction
1745 Whichofthefollowingstructuresshortenduringmusclecontraction?
(a)
myosinfilaments
(b)
flagella
(c)
sarcomeres
(d)
actinfilaments
1746 Whichofthefollowingconditionsbelowislikelytodecreasethelikelihoodof
skeletalmusclecontraction?
(a)
partialdepolarizationoftheTtubulemembrane,suchthattheresting
potentialisclosertozero
(b)
additionofadrugthatblocksCa2+bindingtotroponin
(c)
anincreaseintheamountofATPinthecell
(d)
amutationintropomyosinthatdecreasesitsaffinityfortheactinfilament
1747 Whichofthefollowingstatementsaboutskeletalmusclecontractionisfalse?
(a)
Whenamusclecellreceivesasignalfromthenervoussystem,voltage
gatedchannelsopenintheTtubulemembrane.
(b)
Thechangesinvoltageacrosstheplasmamembranethatoccurwhena
musclecellreceivesasignalfromthenervoussystemcauseaninfluxof
Ca2+intothesarcoplasmicreticulum,triggeringamusclecontraction.
(c)
Achangeintheconformationoftroponinleadstochangesintropomyosin
suchthatitnolongerblocksthebindingofmyosinheadstotheactin
filament.
(d)
Duringmusclecontraction,theZdiscsmoveclosertogetherasthemyosin
headswalktowardtheplusendsoftheactinfilaments.
1748 Doyouagreeordisagreewiththefollowingstatement?Explainyouranswer.
Whenskeletalmusclereceivesasignalfromthenervoussystemto
contract,thesignalfromthemotorneurontriggerstheopeningofa
voltagesensitiveCa2+channelinthemusclecellsplasma
membrane,allowingCa2+toflowintothecell.
1749 Youisolatesomemusclefiberstoexaminewhatregulatesmusclecontraction.
WhenyoubathethemusclefibersinasolutioncontainingATPandCa2+,yousee
musclecontraction(experiment3inTableQ1749).Ca2+isnecessary,as

solutionscontainingATPaloneornothingdonotstimulatecontractionandthus
themuscleremainsinarelaxedstate(experiments1and2inTableQ1749).
Fromwhatyouknowaboutthemechanismofmusclecontraction,fillinyour
predictionsofwhetherthemusclewillbecontractedorrelaxedforexperiments4,
5,and6.Explainyouranswers.

TableQ1749
Extracredit:InwhatstatewouldthemusclebeifyouaddedCa2+butnoATP?

How We Know: Pursuing Motor Proteins


1750 Considertheinvitromotilityassayusingpurifiedkinesinandpurified
polymerizedmicrotubulesshowninFigureQ1750.Thethreepanelsareimages
takenat1secondintervals.Inthisfigure,threemicrotubuleshavebeennumbered
tomakeiteasytoidentifythem.Whichofthefollowingstatementsaboutthis
assayisfalse?

FigureQ1750
(a)

Kinesinmoleculesareattachedbytheirtailstoaglassslide.

(b)
(c)
(d)

Themicrotubulesusedinthisassaymustbepolymerizedusingconditions
thatstabilizetubuleformationorelsetheywouldundergodynamic
instability.
ATPmustbeaddedforthisassaytowork.
AdditionofthenonhydrolyzableATPanalog(AMPPNP)wouldcause
themicrotubulestomovefaster.

1751 Youareinterestedinstudyingkinesinmovements.Youthereforepreparesilica
beadsandcoatthemwithkinesinmoleculessothateachbead,onaverage,has
onlyonekinesinmoleculeattachedtoit.Youaddthesekinesincoatedbeadstoa
preparationofmicrotubulesyouhavepolymerized.Usingvideomicroscopy,you
watchthekinesinmovedownthemicrotubules.
A.
KinesinGFPhasbeenmeasuredtomovealongmicrotubulesatarateof
0.3m/sec,andsinglemoleculestudieshaverevealedthatkinesinmoves
alongmicrotubulesprogressively,witheachstepbeing8nm.Howmany
stepscanthekinesinmoleculetakein4seconds,assumingthatthekinesin
staysattachedtothemicrotubulefortheentire4seconds?
B.
Becauseeachkinesinmoleculeisthoughttotakeapproximately100steps
beforefallingoffthemicrotubule,willyouseeyoursilicabeadsdetach
fromthemicrotubuleduringyour4secondsofobservation?
C.
Whatwouldyoupredictwouldhappentothekinesincoatedsilicabeadsif
youweretoaddAMPPNP(anonhydrolyzableATPanalog)?

CHAPTER 18
THE CELL DIVISION CYCLE

2009 Garland Science Publishing

Overview of the Cell Cycle


181

Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;useeachword
orphraseonlyonce.
Thefourphasesofthecellcycle,inorder,areG1,
__________________,__________________,and
__________________.AcellcontainsthemostDNAafter
__________________phaseofthecellcycle.Acellissmallestin
sizeafter__________________phaseofthecellcycle.Growth
occursin__________________,__________________,and
__________________phasesofthecellcycle.Acelldoesnot
entermitosisuntilithascompleted__________________
synthesis.
DNA
G1
G2

M
nucleotide
organelle

protein
S

182

WhatwouldbethemostobviousoutcomeofrepeatedcellcyclesconsistingofS
phaseandMphaseonly?
(a)
CellswouldnotbeabletoreplicatetheirDNA.
(b)
Themitoticspindlecouldnotassemble.
(c)
Cellswouldgetlargerandlarger.
(d)
Thecellsproducedwouldgetsmallerandsmaller.

183

Amutantyeaststrainstopsproliferatingwhenshiftedfrom25Cto37C.When
thesecellsareanalyzedatthetwodifferenttemperatures,usingamachinethat
sortscellsaccordingtotheamountofDNAtheycontain,thegraphsinFigure
Q183areobtained.

FigureQ183
Whichofthefollowingwouldnotexplaintheresultswiththemutant?
(a)
inabilitytoinitiateDNAreplication
(b)
inabilitytobeginMphase
(c)
inabilitytoactivateproteinsneededtoenterSphase
(d)
inappropriateproductionofasignalthatcausesthecellstoremaininG1
184

Whichofthefollowingeventsdoesnotusuallyoccurduringinterphase?
(a)
Cellsgrowinsize.
(b)
Thenuclearenvelopebreaksdown.
(c)
DNAisreplicated.
(d)
Thecentrosomesareduplicated.

185

Whatwouldhappentotheprogenyofacellthatproceededtomitosisandcell
divisionafterenteringSphasebuthadnotcompletedSphase?Keepinmindthat
highlycondensedchromatin,includingthecentromereregion,isreplicatedlatein
Sphase.Explainyouranswer.

186

Arethestatementsbelowtrueorfalse?Explainyouranswer.
A.
Statement1:Generally,inagivenorganism,theS,G2,andMphasesof
thecellcycletakeadefinedandstereotypedamountoftimeinmostcells.

B.

Statement2:Therefore,thecellcyclecontrolsystemoperatesprimarily
byatimingmechanism,inwhichtheentryintoonephasestartsatimerset
forsufficienttimetocompletetherequiredtasks.Afteragivenamountof
timehaselapsed,amolecularalarmtriggersmovementtothenext
phase.

187

Whichofthefollowingstatementsaboutthecellcycleisfalse?
(a)
Onceacelldecidestoenterthecellcycle,thetimefromstarttofinishis
thesameinalleucaryoticcells.
(b)
AnunfavorableenvironmentcancausecellstoarrestinG1.
(c)
AcellhasmoreDNAduringG2thanitdidinG1.
(d)
ThecleavagedivisionsthatoccurinanearlyembryohaveshortG1andG2
phases.

188

Whichofthefollowingdescriptionsisconsistentwiththebehaviorofacellthat
lacksaproteinrequiredforacheckpointmechanismthatoperatesinG2?
(a)
ThecellwouldbeunabletoenterMphase.
(b)
ThecellwouldbeunabletoenterG2.
(c)
ThecellwouldenterMphaseunderconditionswhennormalcellswould
not.
(d)
ThecellwouldpassthroughMphasemoreslowlythannormalcells.

How We Know: Discovery of Cyclins and Cdks


189

Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;eachwordor
phraseshouldbeusedonlyonce.
Manyfeaturesof__________________cellsmakethemsuitable
forbiochemicalstudiesofthecellcyclecontrolsystem.For
example,thecellsareunusuallylargeandarearrestedina
__________________likephase.Whenthecellsaretriggeredto
resumecycling,thecelldivisionshaveespecially
__________________G1andG2phasesandoccur
__________________.StudieswithXenopuseggsidentifieda
partlypurifiedactivitycalled__________________thatdrivesa
restingXenopusoocyteintoMphase.MPFactivitywasfoundto
__________________duringthecellcycle,althoughtheamount
ofitskinasecomponent,called__________________,remained
constant.TheregulatorycomponentofMPF,called
__________________,hasa__________________effectonMPF
activityandplaysapartinregulatinginteractionswithits
__________________s.ThecomponentsofMPFare
evolutionarily__________________fromyeasttohumans,sothat

thecorrespondinghumangenesare__________________to
functioninyeast.
able
asynchronously
Cdk
conserved
cyclin
divergent
egg
fibroblast
G1
G2

hexokinase
inhibitory
long
M
maturationpromotingfactor
oscillate
PI3kinase
regulin
S

short
sperm
steady
stimulatory
substrate
synchronously
ubiquitin
unable
uniform

1810 MPFactivitywasdiscoveredwhencytoplasmfromaXenopusMphasecellwas
injectedintoXenopusoocytes,inducingtheoocytestoformamitoticspindle.Ina
controlexperiment,Xenopusinterphasecytoplasmwasinjectedintooocytesand
shownnottoinducetheformationofamitoticspindle.Whichofthefollowing
statementsisnotalegitimateconclusionfromthecontrolexperiment?
(a)
Thepiercingoftheoocytemembranebyaneedleisinsufficienttocause
mitoticspindleformation.
(b)
Anincreasedvolumeofcytoplasmisinsufficienttocausemitoticspindle
formation.
(c)
InjectionofextraRNAmoleculesisinsufficienttocausemitoticspindle
formation.
(d)
Componentsofaninterphasenucleusareinsufficienttocausemitotic
spindleformation.
1811 Whichofthefollowingisnotgooddirectevidencethatthecellcyclecontrol
systemisconservedthroughbillionsofyearsofdivergentevolution?
(a)
AyeastcelllackingCdkfunctioncanusethehumanCdktosubstitutefor
itsmissingCdkduringthecellcycle.
(b)
Theaminoacidsequencesofcyclinsinplantsaresimilartotheamino
acidsequencesofcylinsinhumans.
(c)
TheCdkproteinsinhumansshareconservedphosphorylationsiteswith
theCdkproteinsinyeast.
(d)
YeastcellshaveonlyoneCdk,whereashumanshavemanyCdks.

The Cell-Cycle Control System


1812 LevelsofCdkactivitychangeduringthecellcycle,inpart,because
________________.
(a)
theCdksphosphorylateeachother
(b)
theCdksactivatethecyclins

(c)
(d)

Cdkdegradationprecedesentryintothenextphaseofthecellcycle
cyclinlevelschangeduringthecycle

1813 Theconcentrationofmitoticcyclin(Mcyclin)________________.
(a)
risesmarkedlyduringMphase
(b)
isactivatedbyphosphorylation
(c)
fallstowardtheendofMphaseasaresultofubiquitylationand
degradation
(d)
ishighestinG1phase
1814 Youhaveisolatedastrainofmutantyeastcellsthatdividesnormallyat30Cbut
cannotenterMphaseat37C.Youhaveisolateditsmitoticcyclinandmitotic
CdkandfindthatbothproteinsareproducedandcanformanormalMCdk
complexatbothtemperatures.Whichofthefollowingtemperaturesensitive
mutationscouldnotberesponsibleforthebehaviorofthisstrainofyeast?
(a)
inactivationofaproteinkinasethatactsonthemitoticCdkkinase
(b)
inactivationofanenzymethatubiquitylatesMcyclin
(c)
inactivationofaphosphatasethatactsonthemitoticCdkkinase
(d)
adecreaseinthelevelsofatranscriptionalregulatorrequiredfor
producingsufficientamountsofMcyclin
1815 MatchthefollowinglabelstothenumberedlabellinesonFigureQ1815.

FigureQ1815
A.
B.
C.
D.
E.
F.
G.
H.

G1phase
mitoticcyclin
mitoticCdk
Sphase
Sphasecyclin
SphaseCdk
MPF
G2phase

1816 Youhaveisolatedamutantinwhichafractionofthenewcellsdiesoonaftercell
divisionandafractionofthelivingcellshaveanextracopyofoneormore

chromosomes.Whenyougrowthecellsunderconditionsinwhichtheytransitthe
cellcyclemoreslowly,thedefectdisappears,suggestingthatthemitoticspindle
andsegregationmachineryarenormal.Proposeabasisforthedefect.
1817 CellsintheG0state________________.
(a)
donotdivide
(b)
cannotreenterthecellcycle
(c)
haveenteredthisarreststatefromeitherG1orG2
(d)
haveduplicatedtheirDNA
1818 WhatisthemainmoleculardifferencebetweencellsinaG0stateandcellsthat
havesimplypausedinG1?

S Phase
1819 YoucreatecellswithaversionofCdc6thatcannotbephosphorylatedandthus
cannotbedegraded.Whichofthefollowingstatementsdescribesthelikely
consequenceofthischangeinCdc6?
(a)
CellswillenterSphaseprematurely.
(b)
CellswillbeunabletocompleteDNAsynthesis.
(c)
Theoriginrecognitioncomplex(ORC)willbeunabletobindtoDNA.
(d)
Cdc6willbeproducedinappropriatelyduringMphase.
1820 Whichofthefollowingstatementsisfalse?
(a)
DNAsynthesisbeginsatoriginsofreplication.
(b)
Theloadingoftheoriginrecognitioncomplexes(ORCs)istriggeredbyS
Cdk.
(c)
ThephosphorylationanddegradationofCdc6helptoensurethatDNAis
replicatedonlyonceineachcellcycle.
(d)
DNAsynthesiscanonlybeginafterprereplicativecomplexesassembles
ontheORCs.
1821 AttheendofDNAreplication,thesisterchromatidsareheldtogetherbythe
___________.
(a)
kinetochores
(b)
securins
(c)
cohesins
(d)
histones
1822 IrradiatedmammaliancellsusuallystopdividingandarrestataG1checkpoint.
Placethefollowingeventsintheorderinwhichtheyoccur.
A.
productionofp21
B.
DNAdamage
C.
inhibitionofcyclinCdkcomplexes

D.

accumulationandactivationofp53

1823 TheG1DNAdamagecheckpoint________________.
(a)
causescellstoproceedthroughSphasemorequickly
(b)
involvesthedegradationofp53
(c)
isactivatedbyerrorscausedduringDNAreplication
(d)
involvestheinhibitionofcyclinCdkcomplexesbyp21

M Phase
1824 Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;eachwordor
phraseshouldbeusedonlyonce.
Thecellcycleconsistsofanalternationbetween
__________________,whichappearsasaperiodofdramatic
activityunderthemicroscope,andapreparativeperiodcalled
__________________,whichconsistsofthreephasescalled
__________________,__________________,and
__________________.DuringMphase,thenucleusdividesina
processcalled__________________,andthecytoplasmsplitsin
twoinaprocesscalled__________________.Thecellcycle
controlsystemreliesonsharpincreasesintheactivitiesof
regulatoryproteincalled__________________,or
__________________,totriggerSandMphases.Inactivationof
__________________isrequiredtoexitfromMphaseafter
chromosomesegregation.
APC
Cdks
condensation
cyclindependentkinases
cytokinesis
G1phase
G1Cdk

G2phase
interphase
intraphase
kinesins
Mphase
MCdk
meiosis

metaphase
microtubules
mitosis
myosins
Sphase
SCdk

1825 WhichofthefollowingdoesnotoccurduringMphaseinanimalcells?
(a)
growthofthecell
(b)
condensationofchromosomes
(c)
breakdownofnuclearenvelope
(d)
attachmentofchromosomestomicrotubules
1826 Whichofthefollowingstatementsisfalse?

(a)
(b)
(c)
(d)

MitoticCdkmustbephosphorylatedbyanactivatingkinase(Cak)before
itisactive.
PhosphorylationofmitoticCdkbytheinhibitorykinase(Wee1)makesthe
Cdkinactive,evenifitisphosphorylatedbytheactivatingkinase.
ActiveMCdkphosphorylatestheactivatingphosphatase(Cdc25)ina
positivefeedbackloop.
Theactivatingphosphatase(Cdc25)removesallphosphatesfrommitotic
CdksothatMCdkwillbeactive.

1827 Condensins________________.
(a)
aredegradedwhencellsenterMphase
(b)
assembleintocomplexesontheDNAwhenphosphorylatedbyMCdk
(c)
areinvolvedinholdingsisterchromatidstogether
(d)
bindtoDNAbeforeDNAreplicationbegins
1828 Whichofthefollowingstatementsistrue?
(a)
Themitoticspindleislargelymadeofintermediatefilaments.
(b)
Thecontractileringismadelargelyofmicrotubulesandactinfilaments.
(c)
Thecontractileringdividesthenucleusintwo.
(d)
Themitoticspindlehelpssegregatethechromosomestothetwodaughter
cells.

Mitosis
1829 WhichstageofmitosisinananimalcelldoeseachpartofFigureQ1829
represent?

FigureQ1829
1830 FigureQ1830showsalivingcellfromthelungepitheliumofanewtatdifferent
stagesinMphase.Ordertheselightmicrographsintothecorrectsequenceand
identifythestageinMphasethateachrepresents.

FigureQ1830
1831 NamethestageofMphaseinwhichthefollowingeventsoccur.Placethe
numbers18nexttotheletterheadingstoindicatethenormalorderofevents.
A.
alignmentofthechromosomesatthespindleequator
B.
attachmentofspindlemicrotubulestochromosomes
C.
breakdownofnuclearenvelope
D.
pinchingofcellintwo
E.
separationoftwocentrosomesandinitiationofmitoticspindleassembly
F.
reformationofthenuclearenvelope
G.
condensationofthechromosomes
H.
separationofsisterchromatids
1832 Theprincipalmicrotubuleorganizingcenterinanimalcellsisthe____________.
(a)
centrosome
(b)
centromere
(c)
kinetochore
(d)
cellcortex

1833 ExaminetheschematicrepresentationofcentrosomeduplicationinFigureQ18
33.ByanalogywithDNAreplication,wouldyouclassifycentrosomeduplication
asconservativeorsemiconservative?Explainyouranswer.

FigureQ1833

1834 BeforechromosomessegregateinMphase,theyandthesegregationmachinery
mustbeappropriatelyprepared.Indicatewhetherthefollowingstatementsare
trueorfalse.Iffalse,changeasinglenountomakethestatementtrue.
A.
Sisterchromatidsareheldtogetherbycondensinsfromthetimetheyarise
byDNAreplicationuntilthetimetheyseparateatanaphase.
B.
Cohesinsarerequiredtomakethechromosomesmorecompactandthus
topreventtanglingbetweendifferentchromosomes.
C.
Themitoticspindleiscomposedofactinfilamentsandmyosinfilaments.
D.
Microtubuledependentmotorproteinsandmicrotubulepolymerization
anddepolymerizationaremainlyresponsiblefortheorganizedmovements
ofchromosomesduringmitosis.
E.
Thecentromerenucleatesaradialarrayofmicrotubulescalledanaster,
anditsduplicationistriggeredbySCdk.
F.
Eachcentrosomecontainsapairofcentriolesandhundredsoftubulin
ringsthatnucleatethegrowthofmicrotubules.
1835 ThecytoskeletonofananimalcellchangesmarkedlybetweenG1andearlyM
phase(prophase)ofthecellcycle.Foreachofthefollowingsentences,choose
oneoftheoptionsenclosedinsquarebracketsthatbestdescribesthechangesto
thecytoskeletonanditscomponents.
Beforemitosis,thenumberofcentrosomesmust
[increase/decrease].Atthebeginningof[anaphase/prophase]in
animalcells,thecentrosomesseparateinaprocessdrivenpartlyby
interactionsbetweenthe[plus/minus]endsofmicrotubulesarising

fromthetwocentrosomes.Centrosomeseparationinitiatesthe
assemblyofthebipolarmitoticspindleandisassociatedwitha
sudden[increase/decrease]inthedynamicinstabilityof
microtubules.Incomparisonwithaninterphasemicrotubulearray,
amitoticastercontainsa[smaller/larger]numberof
[longer/shorter]microtubules.ExtractsfromMphasecellsexhibit
[increased/decreased/unchanged]ratesofmicrotubule
polymerizationandincreasedfrequenciesofmicrotubule
[shrinkage/growth].Thechangesinmicrotubuledynamicsare
largelydueto[enhanced/reduced]activityofmicrotubule
associatedproteinsand[increased/decreased]activityof
catastrophins.Thenewbalancebetweenpolymerizationand
depolymerizationofmicrotubulesisnecessaryforthemitotic
spindletomovethe[replicatedchromosomes/daughter
chromosomes]tothemetaphaseplate.
1836 Matcheachofthemainclassesofspindlemicrotubulesfromlist1withtheir
functionsandfeaturesfromlist2.

1837 Disassemblyofthenuclearenvelope________________.
(a)
causestheinnernuclearmembranetoseparatefromtheouternuclear
membrane
(b)
resultsintheconversionofthenuclearenvelopeintoproteinfree
membranevesicles
(c)
istriggeredbythephosphorylationofintegrins
(d)
mustoccurforkinetochoremicrotubulestoforminanimalcells
1838 Considerananimalcellthathaseightchromosomes(fourpairsofhomologous
chromosomes)inG1phase.Howmanyofeachofthefollowingstructureswillthe
cellhaveatmitoticprophase?
A.
sisterchromatids
B.
centromeres
C.
kinetochores
D.
centrosomes
E.
centrioles

1839 Whichofthefollowingstatementsaboutkinetochoresistrue?
(a)
Kinetochoresassembleontochromosomesduringlateprophase.
(b)
KinetochorescontainDNAbindingproteinsthatrecognizesequencesat
thetelomereofthechromosome.
(c)
Kinetochoreproteinsbindtothetubulinmoleculesattheminusendof
microtubules.
(d)
Kinetochoresassembleonchromosomesthatlackcentromeres.
1840 Isthefollowingstatementtrueorfalse?
Afterthenuclearenvelopebreaksdown,microtubulesgainaccess
tothechromosomesand,everysooften,arandomlyprobing
microtubulecapturesachromosomeandultimatelyconnectstothe
kinetochoretobecomeakinetochoremicrotubuleofthespindle.
1841 Afrienddeclaresthatchromosomesareheldatthemetaphaseplateby
microtubulesthatpushoneachchromosomefromoppositesides.Whichofthe
followingobservationsdoesnotsupportyourbeliefthatthemicrotubulesare
pullingonthechromosomes?
(a)
thejigglingmovementofchromosomesatthemetaphaseplate
(b)
thewayinwhichchromosomesbehavewhentheattachmentbetween
sisterchromatidsissevered
(c)
thewayinwhichchromosomesbehavewhentheattachmenttoone
kinetochoreissevered
(d)
theshapeofchromosomesastheymovetowardthespindlepolesat
anaphase
1842 Whyshoulditbethatdrugssuchascolchicinethatinhibitmicrotubule
polymerizationanddrugssuchasTaxolthatstabilizemicrotubulesbothinhibit
mitosis?
1843 Whichofthefollowingstatementsabouttheanaphasepromotingcomplex(APC)
isfalse?
(a)
ItpromotesthedegradationofproteinsthatregulateMphase.
(b)
ItinhibitsMCdkactivity.
(c)
Itiscontinuouslyactivethroughoutthecellcycle.
(d)
MCdkstimulatesitsactivity.
1844 Whichofthefollowingstatementsistrue?
(a)
AnaphaseAmustbecompletedbeforeanaphaseBcantakeplace.
(b)
IncellsinwhichanaphaseBpredominates,thespindlewillelongatemuch
lessthanincellsinwhichanaphaseAdominates.
(c)
InanaphaseA,bothkinetochoreandinterpolarmicrotubulesshorten.
(d)
InanaphaseB,microtubulesassociatedwiththecellcortexshorten.

1845 Whenintroducedintomitoticcells,whichofthefollowingisexpectedtoimpair
anaphaseBbutnotanaphaseA?
(a)
anantibodyagainstmyosin
(b)
ATPS,anonhydrolyzableATPanalogthatbindstoandinhibitsATPases
(c)
anantibodyagainstthemotorproteinsthatmovefromtheplusendof
microtubulestotheminusend
(d)
anantibodyagainstthemotorproteinsthatmovefromtheminusendof
microtubulestowardtheplusend
1846 Whichofthefollowingprecedethereformationofthenuclearenvelopeduring
Mphaseinanimalcells?
(a)
assemblyofthecontractilering
(b)
decondensationofchromosomes
(c)
reassemblyofthenuclearlamina
(d)
transcriptionofnucleargenes
1847 AcellwithnuclearlaminsthatcannotbephosphorylatedinMphasewillbe
unableto________________.
(a)
reassembleitsnuclearenvelopeattelophase
(b)
disassembleitsnuclearlaminaatprometaphase
(c)
begintoassembleamitoticspindle
(d)
condenseitschromosomesatprophase
1848 Thelengthsofmicrotubulesinvariousstagesofmitosisdependonthebalance
betweentheactivitiesofcatastrophins,whichdestabilizemicrotubules,and
microtubuleassociatedproteins(MAPs),whichstabilizethem.Ifyoucreated
cellswithanincreasednumberofcatastrophinmolecules,doyoupredictthe
lengthofthemitoticspindlewillbelonger,shorter,orunchanged,relativetothe
correspondingstageofmitosisinwildtypecells?Whatdoyoupredictforacell
withincreasednumbersofMAPs?Explainyourreasoning.
1849 Youhavediscoveredanewproteinthatregulatesmicrotubuledynamics.First,
youisolatedproteinsfromacellularextractthatboundtoatubulinaffinity
column.Youthenseparatedtheproteinsfromeachotherbyloadingthemixture
ofproteinsonanionexchangecolumn,elutingthecolumnwithincreasingsalt
concentrationandcollectingsmallfractionsofproteinastheydrippedfromthe
column.Totestwhethereachfractioncontainedmicrotubuleregulators,you
mixeditwithfluorescenttubulinandpurifiedcentrosomes,andthenanalyzedthe
reactionmicroscopicallytomeasurethesizeoftheastermicrotubulesformed.
Youfoundthatfractions8,9,and10promotedtheformationofunusuallylong
astermicrotubules.Becauseelectrophoreticseparationofthefractionsonagel
revealedaplentifulproteinwithanapparentmolecularweightof98kD,you
namedtheproteinp98.

A.
B.
C.

D.

Doesp98behavelikeaMAPoracatastrophin?
Proposetwowaysinwhichp98mightchangethedynamicbehaviorof
microtubulestoaccountfortheobservedchangeinmicrotubulelength.
Hint:Therearefoursimplepossiblemechanisms.
Videomicroscopyoffluorescenttubulininreactionswithpurified
centrosomesallowedyoutofollowthebehaviorofindividual
microtubulesovertime.Yougraphedthechangesinmicrotubulelengthin
theabsence(FigureQ1851A)andpresence(FigureQ1851B)ofp98.
Fiverepresentativemicrotubulesareshownforeachcondition.Doesp98
altertherateofmicrotubulegrowthorshrinkage?Doesp98alterthe
frequencyofcatastrophes(asuddenandrapiddeclineinmicrotubule
length)orrescues(whenamicrotubuleswitchesfromshrinkingto
growing)?Explainyouranswers.
Afterdemonstratingtheconsequencesofp98onmicrotubuledynamicsin
vitrowiththeuseofpurifiedcomponents,youwanttodeterminewhether
theproteinhasthesameeffectsinacomplexcellularextractthatnaturally
containsp98.Brieflydescribeanexperimentthatwillallowyouto
determinewhatp98normallydoesinmitoticextracts.

FigureQ1851

Cytokinesis
1850 Cytokinesisinanimalcells________________.
(a)
requiresATP

(b)
(c)
(d)

leavesasmallcircularscarofactinfilamentsontheinnersurfaceofthe
plasmamembrane
isoftenfollowedbyphosphorylationofintegrinsintheplasmamembrane
isassistedbymotorproteinsthatpullonmicrotubulesattachedtothecell
cortex

1851 Whichofthefollowingstatementsisfalse?
(a)
Thecleavagefurrowisapuckeringoftheplasmamembranecausedbythe
constrictionofaringoffilamentsattachedtotheplasmamembrane.
(b)
Thecleavagefurrowwillnotbegintoformintheabsenceofamitotic
spindle.
(c)
Thecleavagefurrowalwaysformsperpendiculartotheinterpolar
microtubules.
(d)
Thecleavagefurrowalwaysformsinthemiddleofthecell.
1852 Whichofthefollowingstatementsisfalse?
(a)
Cytokinesisinplantcellsismediatedbythemicrotubulecytoskeleton.
(b)
SmallmembranevesiclesderivedfromtheGolgiapparatusdelivernew
cellwallmaterialforthenewwallofthedividingcell.
(c)
Thephragmoplastformsfromtheremainsofinterpolarmicrotubulesof
themitoticspindle.
(d)
Motorproteinswalkingalongthecytoskeletonareimportantforthe
contractileringthatguidesformationofthenewcellwall.
1853 Whichorganellefragmentsduringmitosis?
(a)
endoplasmicreticulum
(b)
Golgiapparatus
(c)
mitochondrion
(d)
chloroplast

Control of Cell Number and Cell Size


1854 Programmedcelldeathoccurs________________.
(a)
bymeansofanintracellularsuicideprogram
(b)
rarelyandselectivelyonlyduringanimaldevelopment
(c)
onlyinunhealthyorabnormalcells
(d)
onlyduringembryonicdevelopment
1855 Apoptosisdiffersfromnecrosisinthatnecrosis________________.
(a)
requiresthereceptionofanextracellularsignal
(b)
causesDNAtofragment
(c)
causescellstoswellandburst,whereasapoptoticcellsshrinkand
condense
(d)
involvesacaspasecascade

1856 Whichofthefollowingstatementsaboutapoptosisistrue?
(a)
CellsthatconstitutivelyexpressBcl2willbemorepronetoundergo
apoptosis.
(b)
Theprodomainofprocaspasescontainsthecatalyticactivitynecessaryfor
procaspaseactivation.
(c)
BaxandBakpromoteapoptosisbybindingtoprocaspasesinthe
apoptosome.
(d)
Apoptosisispromotedbythereleaseofcytochromecintothecytosol
frommitochondria.
1857 Imaginethatyoucouldmicroinjectcytochromecintothecytosolofbothwild
typecellsandcellsthatwerelackingbothBaxandBak,whichareapoptosis
promotingmembersoftheBcl2familyofproteins.Wouldyouexpectone,both,
orneitherofthecelllinestoundergoapoptosis?Explainyourreasoning.
1858 Thenumberofcellsinanadulttissueoranimaldependsoncellproliferation.
Whatelsedoesitdependon?
1859 Whatisthecauseofthemassiveamountofprogrammedcelldeathofnervecells
(neurons)thatoccursinthedevelopingvertebratenervoussystem,andwhat
purposedoesitserve?
1860 Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;eachwordor
phraseshouldbeusedonlyonce.
Thesurvival,__________________,andsizeofeachcellinan
animalarecontrolledbyextracellularsignalmoleculessecretedby
neighboringanddistantcells.Manyofthesesignalmoleculesbind
toacellsurface__________________andtriggervarious
intracellularsignalingpathways.Oneclassofsignalmolecules,
called__________________,stimulatescelldivisionbyreleasing
themolecularbrakesthatkeepcellsinthe__________________
or__________________phaseofthecellcycle.Membersofa
secondclassofsignalmoleculesarecalled__________________,
becausetheystimulatecellgrowthandanincreaseincellmass.
Thethirdclassofsignalmolecules,called__________________,
inhibits__________________byregulatingmembersofthe
__________________familyofproteins.Inadditiontosuch
stimulatoryfactors,somesignalproteinssuchas
__________________actnegativelyonothercells,inhibitingtheir
survival,growth,orproliferation.

anaphase
annihilation
apoptosis
arrestase
Bcl2
biosynthetic
cascades
caspase
Cdk
cyclin

differentiation
G0
G1
G2
growthfactors
interphase
ligand
M
mitogens

myostatin
nourishment
nutrition
phosphatases
proliferation
receptor
S
survivalfactors
transcription

1861 Ofthefollowingmutations,whicharelikelytocausecellcyclearrest?Ifyou
predictacellcyclearrest,indicatewhetherthecellwillarrestinearlyG1,lateG1,
orG2.Explainyouranswers.
A.
amutationinageneencodingacellsurfacemitogenreceptorthatmakes
thereceptoractiveevenintheabsenceofthemitogen
B.
amutationthatdestroyedthekinaseactivityofSCdk
C.
amutationthatallowedG1Cdktobeactiveindependentlyofits
phosphorylationstatus
D.
amutationthatremovedthephosphorylationsitesontheRbprotein
E.
amutationthatinhibitedtheactivityofRb

CHAPTER 19

SEX AND GENETICS


2009 Garland Science Publishing

The Benefits of Sex


191

Organismsthatreproducesexually________________________.
(a)
mustbehaploid,unlikeorganismsthatreproduceasexually
(b)
canreproduceonlywithapartnerthatcarriesthesamealleles

(c)
(d)

createzygotesthataregeneticallyidenticaltoeachother
undergoasexualreproductivecyclethatinvolvesanalternationofhaploid
cellswiththegenerationofdiploidcells

192

Whichofthefollowingstatementsistrue?
(a)
Anothernameforthefertilizedeggcellisthezygote.
(b)
Diploidorganismsreproduceonlysexually.
(c)
Allsexuallyreproducingorganismsmusthavetwocopiesofevery
chromosome.
(d)
Gameteshaveonlyonechromosome.

193

Whichofthefollowingstatementsisfalse?
(a)
Asexualreproductiontypicallygivesrisetooffspringthataregenetically
identical.
(b)
Mutationsinsomaticcellsarepassedontoindividualsofthenext
generation.
(c)
Sexualreproductionallowsforawidevarietyofgenecombinations.
(d)
Gametesarespecializedsexcells.

194

Somaticcells___________________________.
(a)
arenotnecessaryforsexualreproductioninalleucaryoticorganisms
(b)
areusedtoproducegermlinecellswhenorganismsreachsexualmaturity
(c)
leavenoprogeny
(d)
donotcontainsexchromosomes

195

Whichofthefollowingstatementsaboutthebenefitsofsexualreproductionis
false?
(a)
Sexualreproductionpermitsenhancedsurvivalbecausethegametesthat
carryallelesenhancingsurvivalinharshenvironmentsareused
preferentiallyduringfertilization.
(b)
Unicellularorganismsthatcanundergosexualreproductionhavean
increasedabilitytoadapttoharshenvironments.
(c)
Sexualreproductionreshufflesgenes,whichisthoughttohelpspecies
surviveinnovelorvaryingenvironments.
(d)
Sexualreproductioncanspeedtheeliminationofdeleteriousalleles.

196

Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;eachwordor
phrasemaybeusedmorethanonce.
Toreproducesexually,anorganismmustcreatehaploid
__________________cells,or__________________,from
diploidcellsviaaspecializedcelldivisioncalled
__________________.Duringmating,thefathershaploidcells,

called__________________inanimals,fusewiththemothers
haploidcells,called__________________.Cellfusionproducesa
diploidcellcalleda__________________,whichundergoesmany
roundsofcelldivisiontocreatetheentirebodyofthenew
individual.Thecellsproducedfromtheinitialfusioneventinclude
__________________cellsthatformmostofthetissuesofthe
bodyaswellasthe__________________linecellsthatgiverise
tothenextgenerationofprogeny.
allele
bivalent
eggs
gametes

germ
meiosis
mitosis
pedigree

pollen
somatic
sperm
zygote

197

Whyissexualreproductionmorebeneficialtoaspecieslivinginanunpredictable
environmentthantoonelivinginaconstantenvironment?

198

Isthefollowingstatementtrueorfalse?Explain.
Somaticcellsleavenoprogenyandthus,inanevolutionarysense,
existonlytohelpcreate,sustain,andpropagatethegermcells.

199

Sexualreproductionisalargedrainonthelimitedresourcesofanindividual.
Nonetheless,sexualreproductioniscommon.Infact,toallowsexual
reproduction,organismshaveevolvedmanyelaborateanatomicalstructures,
cellularprocesses,andchemicalsignals.Forexample,flowersexistentirelyto
furtherthegoalofsexualreproduction,andmanyplantshaveenlistedthehelpof
beesandbirdstoaidinthedisseminationoftheirgermcells.Describeonereason
whymostmulticellularorganismshaveevolvedtoreproducesexuallyinsteadof
relyingsolelyonasexualreproduction.

Meiosis and Fertilization


1910 Indicatewhethereachofthefollowingistrueformeiosis,mitosis,both,or
neither.
A.
formationofabivalent
B.
geneticallyidenticalproducts
C.
condensationofchromosomes
D.
segregationofallpaternalchromosomestoonecell
E.
involvementofDNAreplication
1911 Meiosisisahighlyspecializedcelldivisioninwhichseveraleventsoccurina
preciselydefinedorder.Pleaseorderthemeioticeventslistedbelow.
1.
lossofcohesinsnearcentromeres

2.
3.
4.
5.
6.
7.
8.

chromatidpairing
chromosomecondensation
chromosomereplication
degradationofcohesinsboundtochromosomearms
formationofchiasmata(chiasmata=pluralofchiasma)
homologpairing
alignmentofchromosomesatthemetaphaseplate

1912 Foreachofthefollowingsentences,chooseoneoftheoptionsenclosedinsquare
bracketstomakeacorrectstatement.
Startingwithasinglediploidcell,mitosisproduces[two/four]
[identical/different][haploid/diploid]cells,whereasmeiosisyields
[two/four][identical/different][haploid/diploid]cells.Thisis
accomplishedinmeiosisbecauseasingleroundofchromosome
[replication/segregation]isfollowedbytwosequentialroundsof
[replication/segregation].Mitosisismorelikemeiosis[I/II]than
meiosis[I/II].InmeiosisI,thekinetochoresonsisterchromatids
behave[independently/coordinately]andthusattachto
microtubulesfromthe[same/opposite]spindle.Thecohesin
mediatedgluebetween[chromatids/homologs]isregulated
differentlynearthecentromeresthanalongthechromosomearms.
Cohesionislostfirstatthe[centromeres/arms]toallow
segregationof[chromatids/homologs]andislostlateratthe
[centromeres/arms]totriggersegregationof
[chromatids/homologs].
1913 Intheabsenceofrecombination,howmanygeneticallydifferenttypesofgamete
cananorganismwithfivehomologouschromosomepairsproduce?
(a)
5
(b)
10
(c)
32
(d)
64
1914 Whichofthefollowingstatementsmostcorrectlydescribesmeiosis?
(a)
MeiosisinvolvestworoundsofDNAreplicationfollowedbyasinglecell
division.
(b)
MeiosisinvolvesasingleroundofDNAreplicationfollowedbyfour
successivecelldivisions.
(c)
MeiosisinvolvesfourroundsofDNAreplicationfollowedbytwo
successivecelldivisions.
(d)
MeiosisinvolvesasingleroundofDNAreplicationfollowedbytwo
successivecelldivisions.

1915 Adiploidcellcontaining32chromosomeswillmakeahaploidcellcontaining
___chromosomes.
(a)
8
(b)
16
(c)
30
(d)
64
1916 Imagineadiploidsexuallyreproducingorganism,Diploidussexualis,that
containsthreepairsofchromosomes.Thisorganismisunusualinthatno
recombinationbetweenhomologouschromosomesoccursduringmeiosis.
A.
Assumingthatthechromosomesaredistributedindependentlyduring
meiosis,howmanydifferenttypesofspermoreggcellscanasingle
individualofthisspeciesproduce?
B.
Whatisthelikelihoodthattwosiblingsofthisspecieswillbegenetically
identical?Youcanassumethatthehomologouschromosomesofeach
parentaredifferentfromoneanotherandfromtheircounterpartsinthe
otherparent.
1917 Youhavereceivedexactlyhalfofyourgeneticmaterialfromyourmother,who
receivedexactlyhalfofhergeneticmaterialfromhermother(yourgrandmother).
A.
Explainwhyitisunlikelythatyoushareexactlyonequarterofyour
geneticmaterialwithyourgrandmother,andinsteaditismoreaccurateto
saythatingeneralpeoplereceiveanaverageofonequarteroftheir
geneticendowmentfromeachgrandparent.
B.
Considerageneonchromosome3thatyoureceivedfromyour
grandmother.Isitlikelyyoureceivedanentirechromosome3fromyour
grandmother?Whyorwhynot?
C.
Whatportionofyourgeneticmaterialdoyousharewithyoursibling?
Youraunt?Yourcousin?
1918 Youexamineawormthathastwogenders:malesthatproducespermand
hermaphroditesthatproducebothspermandeggs.Thediploidadulthasfour
homologouspairsofchromosomesthatundergoverylittlerecombination.Given
achoice,thehermaphroditesprefertomatewithmales,butjusttoannoythe
worm,youpluckahermaphroditeoutofthewildandfertilizeitseggswithits
ownsperm.Assumingthatalltheresultingoffspringareviable,whatfractiondo
youexpecttobegeneticallyidenticaltotheparentworm?Assumethateach
chromosomeintheoriginalhermaphroditeisgeneticallydistinctfromits
homolog.
(a)
All
(b)
None
(c)
1/16
(d)
1/256

1919 Whichofthefollowingstatementsaboutmeiosisistrue?
(a)
Duringmeiosis,thepaternalchromosomespairwiththematernal
chromosomesbeforeliningupatthemetaphaseplate.
(b)
Unicellularorganismsthathaveahaploidstateundergomeiosisinsteadof
mitosisduringcelldivision.
(c)
Meiosisproducesfourgeneticallyidenticalcells.
(d)
Ingeneral,meiosisisfasterthanmitosis.
1920 FigureQ1920isadiagramofchromosomesduringmeiosis.

FigureQ1920
A.
B.

Onthediagram,indicatewhichlabellinescorrespondtothefollowing
items:(1)sisterchromatids,(2)homologouschromosomes,(3)bivalent,
(4)chiasma.
Onthefigure,drawassmallcircles(oooo)thecohesingluethatis
releasedinmeioticdivisionI,anddrawassmallcrosses(xxxx)the
cohesingluethatisreleasedinmeioticdivisionII.

1921 Duringrecombination________________________.
(a)
sisterchromatidsundergocrossingoverwitheachother
(b)
chiasmataholdchromosomestogether
(c)
onecrossovereventoccursforeachpairofhumanchromosomes
(d)
thesynaptonemalcomplexkeepsthesisterchromatidstogetheruntil
anaphaseII
1922 Afterthefirstmeioticcelldivision________________________.
(a)
twohaploidgametesareproduced

(b)
(c)
(d)

cellsareproducedthatcontainthesamenumberofchromosomesas
somaticcells
thenumberofchromosomeswillvarydependingonhowthepaternaland
maternalchromosomesalignatthemetaphaseplate
DNAreplicationoccurs

1923 Meiosisincludesarecombinationcheckpointthatisanalogoustothecheckpoints
incellcycleprogression.DoublestrandedbreaksintheDNAinitiate
recombinationinmeiosis.ThebrokenendofaDNAmoleculefindsthe
correspondingsequenceonahomologouschromosomeandexchangesa
chromosomalsegmentwithitshomolog,therebyrepairingthebreak.Ongoing
recombinationsendsanegativeregulatorysignalthatpreventscellsfromentering
meioticdivisionI.
A.
Mutationsinseveralgenesinactivatetherecombinationcheckpoint.What
doyoupredictwillhappenifacellproceedsthroughmeioticdivisionI
beforecompletingrecombination?
B.
Whatwillhappenifacellfailstoinitiaterecombinationandproceeds
throughmeioticdivisionI?MeioticdivisionII?
1924 Insomefungi,celldivisionduringmeiosisgivesrisetoanorderedsporesac
containingarowoffourhaploidspores,asshowninFigureQ1924A.The
positionofeachsporewithinthesacreflectsitsrelationtoitsneighbors;inother
words,sporesthatresultfromthesamemeiosisIIdivisionarepositionednextto
eachother.Younoticethatastrainofthefungusproducedbycrossingadark
coloredstrainwithalightcoloredstraingivesrisemostlytosporesacsasshown
inFigureQ1924B,withafewsporesacslikethoseinFigureQ1924C.Indicate
whetherthefollowingstatementsarecorrect.Explainyourreasoning.

FigureQ1924

A.
B.
C.
D.
E.

MeiosisIandmeiosisIIinthefungusoccurinthereverseorderfromthat
whichoccursinhumans.
RecombinationinthefunguscanoccurduringprophaseI.
RecombinationinthefunguscannotoccurduringprophaseII.
ThesporesacsinpanelCresultfromrecombinationbetweenthe
centromereandthegeneresponsibleforsporecolor.
Recombinationhasoccurredbetweenthegeneresponsibleforsporecolor
andtheendofthechromosomearm.

1925 Inmammals,therearetwosexchromosomes,XandY,whichbehavelike
homologouschromosomesduringmeiosis.NormalmaleshaveoneX
chromosomeandoneYchromosome,andnormalfemaleshavetwoX
chromosomes.MaleswithanextraYchromosome(XYY)arefoundoccasionally.
WhichofthefollowingcouldgiverisetosuchanXYYmale?Explainyour
answer.
(a)
nondisjunctioninthefirstmeioticdivisionofspermatogenesis;normal
meiosisinthemother
(b)
nondisjunctioninthesecondmeioticdivisionofspermatogenesis;normal
meiosisinthemother
(c)
nondisjunctioninthefirstmeioticdivisionofoogenesis;normalmeiosisin
thefather
(d)
nondisjunctioninthesecondmeioticdivisionofoogenesis;normal
meiosisinthefather
1926 Whichofthefollowingwouldnotleadtoaneuploidyduringmeiosis?
(a)
sisterchromatidssegregatinginappropriately
(b)
nonsisterchromatidssegregatinginappropriately
(c)
areciprocalrearrangementofpartsbetweennonhomologous
chromosomes(e.g.,theleftarmofchromosome2exchangingplaceswith
therightarmofchromosome3)
(d)
anextrasetofchromosomesproducedduringSphase(e.g.,ifpaternal
chromosome3werereplicatedtwice)
1927 Asinglenondisjunctioneventduringmeiosis___________________.
(a)
willblockrecombination
(b)
willoccuronlyduringmeiosisII
(c)
cannotoccurwithsexchromosomes
(d)
willinvolvetheproductionoftwonormalgametesifitoccursduring
meiosisII
1928 Duringfertilizationinhumans,_______________________.
(a)
awaveofCa2+ionsisreleasedinthefertilizedeggscytoplasm
(b)
onlyonespermbindstotheunfertilizedegg

(c)
(d)

aspermmovesinarandomfashionuntilitencountersanegg
severalspermpronucleicompeteinthecytoplasmtofusewiththeegg
nucleus

1929 Doyouagreeordisagreewiththefollowingstatement?Explainyouranswer.
Ifadiploidorganismhas16chromosomes(andthus8pairsof
homologouschromosomes),thatorganismcanproduceonly28
geneticallydifferentgametes.

Mendel and the Laws of Inheritance


1930 WhichofthefollowingstatementsaboutMendelsexperimentsisfalse?
(a)
Thepeaplantscouldundergobothcrossfertilizationandselffertilization.
(b)
ThetruebreedingstrainswerehomozygousforthetraitsthatMendel
examined.
(c)
Theeggcancarryeithertheallelefromthematernalorthepaternal
chromosome.
(d)
AlltraitsthatMendelstudiedwererecessive.
Questions1931to1934usethefollowinginformationandFigureQ1931.These
questionsmaybeusedindependently,orasagroup.
FigureQ1931diagramsoneofMendelsexperimentsusingtheroundandwrinkledseed
traits.

FigureQ1931
1931 Whichofthefollowingcouldbeconsideredatruebreedingstrainfortheseed
shapephenotype?(SeeFigureQ1931.)
(a)
alloftheroundseededplantsproducedintheF2generation
(b)
allofthewrinkleseededplantsproducedintheF2generation
(c)
alloftheroundseededplantsproducedintheF1generation
(d)
halfoftheroundseededplantsproducedintheF2generation
1932 IfyoucrossedtheroundseededplantsobtainedintheF1generationwithatrue
breedingstrainofroundseededplants,howmanywrinkleseededplantswould
youexpecttoobtaininthenextgeneration?(SeeFigureQ1931.)
(a)
none
(b)
25%
(c)
75%
(d)
all
1933 IfyoucrossedtheroundseededplantsobtainedintheF1generationwithatrue
breedingstrainofwrinkleseededplants,howmanyroundseededplantswould
youexpecttoobtaininthenextgeneration?(SeeFigureQ1931.)
(a)
25%
(b)
50%
(c)
75%
(d)
100%
1934 Whichofthefollowingstatementsabouttheroundseededpeaplantsobtainedin
theF2generationisfalse?(SeeFigureQ1931.)
(a)
Theseplantsarephenotypicallyidenticalforseedshape.
(b)
Twothirdsoftheseplantsareexpectedtobeheterozygousfortheseed
shapeallele.
(c)
Weexpect25%oftheseplantstobehomozygousfortheseedshape
allele.
(d)
Iftheseplantswerecrossedtowrinkleseededplants,someoftheseplants
wouldproduceonlyroundseededplants.
1935 WhichofthefollowingreasonswasessentialforMendeltodisprovethetheoryof
blendedinheritance?
(a)
ThetraitsthatMendelexaminedallinvolvedgenesthatdidnotdisplay
linkage.
(b)
ThetraitsthatMendelexaminedallinvolvedthereproductivestructuresof
thepeaplant.
(c)
Mendelpioneeredtechniquespermittingthefusionofmaleandfemale
gametesfromthesameplanttoproduceazygote.

(d)

ThetraitsthatMendelexaminedinvolvedanallelethatwasdominantand
anallelethatwasrecessive.

1936 WhichofthefollowingreasonswasessentialforMendelslawofindependent
assortment?
(a)
AllthetraitsthatMendelexaminedinvolvedgenesthatdidnotdisplay
linkage.
(b)
SeveralofthephenotypesthatMendelexaminedinvolvedcolor.
(c)
Mendelobservedchromosomalsegregationinpeaplantcells.
(d)
Mendelcarriedouthisexperimentsonplantsandnotonfungi.
1937 Isthefollowingstatementtrueorfalse?Explain.
Thephenotypeofanorganismreflectsalloftheallelescarriedby
thatindividual.
1938 WithrespecttogeneEonthechromosomedrawninFigureQ1938,whichgene
isleastlikelytobehaveaccordingtoMendelslawofindependentassortment?
Explainyouranswer.

FigureQ1938
1939 Cysticfibrosisresultsfrommutationsinasinglegenethatliesonchromosome7.
Onlyhomozygousmutant(ff)individualsaresick;homozygouswildtype(FF)
andheterozygous(Ff)individualsarehealthy.Ahealthymarriedcouplehasone
childwithcysticfibrosisandthewifeispregnantwithasecondchild.
A.
Whatisthegenotypeofthemother?Thefather?
B.
Whatisthechancethatthesecondchildwillhavecysticfibrosis?
1940 Sicklecellanemiaiscausedbyamutantalleleofahemoglobingene.Individuals
withtwomutantalleleshavesicklecellanemia.Individualshomozygousand

heterozygousforthemutantgenearemoreresistanttomalariathanthosewith
twowildtypealleles.Isthismutationdominant,recessive,orcodominant?
1941 YourfriendhasobtainedsomepeaseedsfromtheAbbeyofSt.ThomasinBrno,
whereGregorMendelworked.Heisveryexcitedbecausenotonlydidheobtain
someyellowandgreenpeaseedsfromtruebreedingplants(liketheonesusedin
Mendelsfamousexperiment),hewasalsoabletoobtainsomepurplepeaseeds
fromatruebreedingplant.First,yourfriendtakesthetruebreedingyellowand
greenpeaseeds,repeatsthecrossthatGregorMendeldid,andobtainsthesame
results:hesees100%yellowseededpeaplantsintheF1generation,and75%
yellowseededpeaplantsand25%greenseededpeaplantsintheF2generation.
HisresultsareillustratedinFigureQ1941A.Yourfriendthendecidestosetup
twomorecrosses.Forcross#2,hecrossesthetruebreedingpurpleseededpea
plantstothetruebreedingyellowseededpeaplants.Theresultsfromthiscross
areshowninFigureQ1941B.Next,forcross#3,hecrossesthetruebreeding
purpleseededpeaplantstothetruebreedinggreenseededpeaplants.These
resultsareshowninFigureQ1941C.

FigureQ1941
Giventheseresults,ifyouweretotakethepurpleseededpeaplantsproducedin
theF1generationincross#2andcrossthemtothepurpleseededpeaplants
producedintheF1generationofcross#3,whatdoyouexpectthatthephenotype
oftheprogenywouldlooklike?Explainyouranswer.
1942 Youaregiventwotruebreedingstrainsofhamster.Onestrainhaswhitefurcolor
andtheotherhasadarkbrownfurcolor.Whenyoucrossthewhitefurstrainto
thedarkbrownfurstrain,youobtainF1progenythathavealightbrownfurcolor.
WhenyoucrosstheF1progenywitheachother,25%oftheF2generationhave
whitefur,25%havedarkbrownfur,and50%havelightbrownfur.Howmany
genescrucialforfurcolorationdifferbetweenthetwostartingstrains?Explain
youranswer.
Extracredit:Proposeamolecularmechanismforhowfurcolorisdeterminedin
thisspeciesofhamster.
1943 Lossoffunctionmutations________________________.
(a)
causetheproductionofproteinsthatareactiveininappropriate
circumstances
(b)
willusuallyshowaphenotypewhenheterozygous
(c)
areonlypresentinapopulationatbarelydetectablelevels
(d)
areusuallyrecessive

Genetics as an Experimental Tool


1944 Conditionalallelesaremutantgeneversionsencodingproteinsthatcanfunction
normallyatthepermissiveconditionbutaredefectiveattherestrictivecondition.
Onecommonlyusedconditionistemperature.Conditionalallelesareespecially
usefultogeneticistsbecausetheypermitthestudyofessentialgenes.Atthe
permissivetemperature,theorganismlivesnormally.Whentheorganismis
shiftedtothenonpermissivetemperature,theeffectofinactivatingthegenecan
bestudied.WhichofthethreetypesofmutationshowninFigureQ1944ismost
likelytoleadtoaconditionalallele?Explainyouranswer.

FigureQ1944
1945 YouperformedageneticscreeninC.elegansandfoundtwomutations(#1and
#2)thatcauseantisocialbehavior.Youwanttolearnwhetherthesearemutations
inthesamegeneordifferentgenes,soyoucrossmutant#1andmutant#2
togethertoperformacomplementationtest.Imaginethatthemutationsarein

differentgenes:mutation#1isingeneMandmutation#2ingeneN.

FigureQ1945
A.

B.
C.
D.

Whatistheoutcomeofacomplementationtestif#1and#2areboth
recessivemutations(mandn,respectively)?Fillintheemptyovalin
FigureQ1945Aandindicatewhethertheoffspringexhibitssocialor
antisocialbehavior.
Whatistheoutcomeif#1isdominantand#2isrecessive(M*andn)?Fill
intheemptyovalinFigureQ1945Bandindicatewhethertheoffspring
exhibitssocialorantisocialbehavior.
ForthecaseinA,wouldthephenotypeoftheoffspringdifferifthetwo
mutationswereinthesamegene?
ForthecaseinB,wouldthephenotypeoftheoffspringdifferifthetwo
mutationswereinthesamegene?Arecomplementationtestsusefulfor
analyzingdominantmutations?

1946 Doyouagreeordisagreewiththefollowingstatement?Explainyouranswer.
Atraitthatisfoundatalowfrequencyinthepopulationhastobe
arecessivetrait.
1947 Youarestudyingadiploidyeaststrainthatnormallyusesglucoseasanenergy
sourcebutcanusemaltosewhennoglucoseispresent.Youareinterestedin
understandinghowthisyeaststrainmetabolizesmaltoseasanalternativeenergy
source.Youisolatethegenesinvolvedinmaltosemetabolismbyscreeningfor
yeastthatcannotgrowwhenmaltoseisthesoleenergysource.Youfindsix
differentmutants,allofwhicharerecessive,andnametheseallelesmal1,mal2,
mal3,mal4,mal5,andmal6.Next,youisolategametesfromthehomozygous
diploidmutantyeaststrainsandperformcrossesbetweenthedifferentstrainsto
docomplementationanalysis,becauseyouwishtodeterminewhetherthe
mutationsarelikelytoaffectthesameordifferentgenes.Yourresultsareshown
inTableQ1947.

TableQ1947Complementationanalysisofmalgenes.
Inhowmanygenesareyoulikelytohaveisolatedmutations?Whichallelesseem
toaffectthesamegenes?Explainyouranswer.
1948 GeneAislocatedneargeneBonchromosome13inhumans.Amutationinthe
germlineofanindividualwiththehaplotypeABgeneratesgameteswiththe
genotypeAb.Manydescendentsofthisfounderindividualcarrythebmutation,
whichpredisposescarrierstohighbloodpressure.Initially,alldescendentswho
inheritthebmutationalsoinherittheneighboringAallele.Throughthe
generations,fewerandfewerdescendentswiththebmutationcarrytheAallele,
andinsteadtheyhavetheaallele.(IndividualswithAandaareequallyhealthy
andfit.)ExplainhowthebandAallelesareseparated.
1949 ShowninFigureQ1949isageneticpedigreeofafamilywithseveralmembers
affectedbyaheritabledisease.Affectedindividualsareshowninblackand
healthyindividualsareshowninwhite.Malesareshownasboxesandfemalesas
circles.Canasinglemutationexplainthepatternofinheritance?Isthemutation
responsibleforthediseasedominantorrecessive?Isthemutationcarriedonthe
Xchromosome,theYchromosome,oranautosome?

FigureQ1949
1950 Thesinglenucleotidepolymorphismsfoundinthehumanpopulation
__________________.
(a)
areimportantforgeneticmappingbecausetheyrepresentmutationsin
genesimportantforhumandisease
(b)
arerarelyfoundamongbloodrelatives
(c)
canbelinkedintohaplotypeblocks
(d)
arosemainlyduringthepast10,000years

How We Know: Using SNPs to Get a Handle on Human Disease


1951 Youaretryingtomapahumangenethoughttobeinvolvedincatallergies.
Becauseyouknow
thisgeneison
chromosome20,
youdecidetoexamine
thelinkageof
severalSNPslocated
onchromosome20
withrespecttothe
geneinvolvedin
catallergies.Youhave

obtainedDNAfrom10individuals,andyouknowwhethertheyareallergicto
cats.YourSNPresultsareshowninTableQ1951.

TableQ1951SNPtestsforchromosome20.(+indicatesthepresenceofSNP.)
A.
B.

WhichSNPismostlikelytobetightlylinkedtothegeneinvolvedincat
allergies?Explainyouranswer.
OftheSNPstestedabove,whichislikelytobethenextclosesttothegene
responsiblefortheallergicstate?Why?

1952 Anytwohumanbeingstypicallyhaveanestimated0.1%differenceintheir
nucleotidesequences,whichisequivalenttoabout3millionnucleotide
differences.ThesedifferencesarethebasisoftheSNPsusedtoconstructgenetic
linkagemaps.SomeoftheseSNPsactuallylieintheregionoftheDNAthat
codesfortheprotein,yettheyhavenoeffectonthephenotypeofindividuals
carryingtheSNPonbothhomologouschromosomes.ExplainhowsomeSNPs
canliewithintheportionoftheDNAthatcodesfortheproteinandyethaveno
discernibleeffectontheproteinsactivity.
1953 FindingcoinheritanceofaSNPvariantandadiseasetellsscientiststhat
____________________.
(a)
everybodywhocarriesthisSNPwillgetthedisease
(b)
sequenceswithintheSNPcausethedisease
(c)
ageneimportantforcausingthediseaseislinkedtotheSNP
(d)
SNPsonotherchromosomeswillnotbecoinheritedwiththedisease
1954 YoudecidetocarryoutgeneticassociationstudiesandidentifyaSNPvariantthat
isfoundsignificantlymoreofteninindividualswhohaveschizophreniathanin
thosewhoarenotaffected.ThisSNPisfoundwithinanintronoftheSZPgene.
A.
CanyoudeducethatanabnormalityoftheSZPgeneisacauseof
increasedriskofschizophrenia?
B.
CanyousaywhethertheSNPvariantitselfisacause?

CHAPTER 20
CELLULAR COMMUNITIES: TISSUES, STEM
CELLS, AND CANCER

2009 Garland Science Publishing

Extracellular Matrix and Connective Tissues


201

Bothmulticellularplantsandanimalshave_____________________.
(a)
cellscapableoflocomotion
(b)
cellswithcellwalls
(c)
acytoskeletoncomposedofactinfilaments,microtubules,and
intermediatefilaments
(d)
tissuescomposedofmultipledifferentcelltypes

202

Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;useeachword
orphraseonlyonce.
Plantsaresedentaryandthustheircellshavedifferentneedsfrom
thoseofcellsfoundinmotileanimals.Forexample,inplantcells,
__________________generatestheturgorpressurethatdrivescell
growth.Plantshavecellwalls,butcellgrowthispossibleinthe
developingtissuebecausethe__________________cellwallsare
expandable.The__________________cellwallsaredeposited
oncegrowthhasstopped,andcanbespeciallyadaptedtotheir
function.Fibersmadefrom__________________(themost
abundantorganicmacromoleculeonEarth)arefoundinplantcell
walls,andprovidetensilestrength.Inwoodytissues,the
__________________inthecellwallsmakesthetissuemorerigid
andwaterproof.Thedepositionofthecellwallisdirectedbythe
__________________cytoskeleton.
cellulose
collagen
epidermis
nuclear
pectin

203

lignin
membranous
osmosis
lamin
primary

secondary
microtubule
tertiary
actin

Whichofthefollowingstatementsaboutplantcellwallsistrue?
(a)
Themicrotubulecytoskeletondirectstheorientationinwhichcelluloseis
depositedinthecellwall.

(b)
(c)
(d)
204

Themolecularcomponentsofthecellwallarethesameinallplant
tissues.
Becauseplantcellwallsarerigid,theyarenotdepositeduntilthecellhas
stoppedgrowing.
Thecellulosefoundincellwallsisproducedasaprecursormoleculein
thecellanddeliveredtotheextracellularspacebyexocytosis.

IndicatethedirectioninwhichtheplantcellshowninFigureQ204ismostlikely
togrow.Theblacklinesindicatethedirectionofthecellulosemicrofibrilsaround
thecell.Explainyouranswer.

FigureQ204
205

Whichofthefollowingmoleculesarenotfoundinplants?
(a)
cellulose
(b)
lignin
(c)
collagen
(d)
pectin

206

Indicatewhetherthefollowingmoleculesarefoundinplants,animals,orboth.
A.
intermediatefilaments
B.
cellwalls
C.
microtubules
D.
cellulose
E.
collagen

207

Whichofthefollowingstatementsaboutanimalconnectivetissuesistrue?
(a)
Enzymesembeddedintheplasmamembranesynthesizethecollagenin
theextracellularmatrixextracellularly.
(b)
Inconnectivetissue,theintermediatefilamentswithinthecellsare
importantforcarryingthemechanicalload.
(c)
Cellscanattachtoacollagenmatrixbyusingfibronectin,anintegral
membraneprotein.
(d)
Proteoglycanscanresistcompressionintheextracellularmatrix.

208

Amajordistinctionbetweentheconnectivetissuesinananimalandothermain
tissuetypessuchasepithelium,nervoustissue,ormuscleis_______________.
(a)
theabilityofconnectivetissuecellssuchasfibroblaststochangeshape
(b)
theamountofextracellularmatrixinconnectivetissues
(c)
theabilityofconnectivetissuestowithstandmechanicalstresses

(d)
209

thenumerousconnectionsthatconnectivetissuecellsmakewitheach
other

Whatarethemainstructuresprovidingtensilestrengthinthefollowing?
A.
animalconnectivetissue
B.
animalepidermis
C.
plantcellwalls

2010 Doyouagreeordisagreewiththefollowingstatement?Explainyouranswer.
Likemanyotherextracellularproteins,newlysynthesizedcollagen
moleculesundergoposttranslationalprocessinginsidethecellto
convertthemintotheirmatureform;theyarethensecretedand
selfassembleintofibrilsintheextracellularspace.
2011 Fibroblastsorganizethecollagenoftheextracellularmatrixby______________.
(a)
cuttingandrejoiningthefibrils
(b)
processingprocollagenintocollagen
(c)
twistingfibrilstogethertomakeropelikefibers
(d)
pullingthecollagenintosheetsorcablesafterithasbeensecreted
2012 MatchthefourletteredlinesinFigureQ2012withtheappropriatenumbered
label.

FigureQ2012
1.integrin
2.actin
3.collagen
4.fibronectin

2013 Whichofthefollowingstatementsaboutintegrinsisfalse?
(a)
Integrinsuseadaptorproteinstointeractwiththemicrotubule
cytoskeleton.
(b)
Integrinscanswitchtoanactivatedstatebybindingtoanextracellular
matrixmolecule.
(c)
Integrinscanswitchtoanactivatedstatebybindingtoanintracellular
protein.
(d)
Anactivatedintegrinmoleculetakesonanextendedconformation.
2014 Proteoglycansintheextracellularmatrixofanimaltissues________________.
(a)
chieflyprovidetensilestrength
(b)
allowcartilagetoresistcompression
(c)
arelinkedtomicrotubulesthroughtheplasmamembrane
(d)
arepolysaccharidescomposedofglucosesubunits
2015 Whichofthefollowingstatementsisfalse?
(a)
Proteoglycanscanactasfilterstoregulatewhichmoleculespassthrough
theextracellularmedium.
(b)
Thenegativechargeassociatedwithproteoglycansattractscations,which
causewatertobesuckedintotheextracellularmatrix.
(c)
Proteoglycansareamajorcomponentofcompactconnectivetissuesbut
arerelativelyunimportantinwaterytissuessuchasthejellylikesubstance
intheinterioroftheeye.
(d)
Glycosaminoglycansarecomponentsofproteoglycan.

Epithelial Sheets and Cell Junctions


2016 Foreachofthefollowingsentences,fillintheblankswiththebestwordorphrase
selectedfromthelistbelow.Notallwordsorphraseswillbeused;useeachword
orphraseonlyonce.
__________________ join the intermediate filaments in one cell to
those in the neighboring cell. __________________ anchor
intermediate filaments in a cell to the extracellular matrix.
__________________ involve cadherin connections between
neighboring cells and are anchorage sites for actin filaments.
__________________permit the passage of small molecules from
one cell to its adjacent cell. __________________ prevent the
leakage of molecules between adjacent cells.
adherens junctions
desmosomes

gap junctions
hemidesmosomes

highway junctions
tight junctions

2017 LabelthefivedifferenttypesofcellcelljunctionshowninFigureQ2117,and
identifytheapicalandbasalsurfacesoftheepithelium.

Figure Q20-17
2018 Matchthemolecules(list1)withthecellstructuresinwhichtheyareinvolved
(list2).Acellstructuremaybelistedmoreorlessthanonce.

2019 Abasallamina______________________.
(a)
isathinlayerofconnectivetissuecellsandmatrixunderlyingan
epithelium
(b)
isathinlayerofextracellularmatrixunderlyinganepithelium
(c)
isattachedtotheapicalsurfaceofanepithelium
(d)
separatesepithelialcellsfromeachother
2020 Tightjunctions______________________.
(a)
allowsmallwatersolublemoleculestopassfromcelltocell
(b)
interactwiththeintermediatefilamentsinsidethecell

(c)
(d)

areformedfromclaudinsandoccludins
arefoundincellsinconnectivetissues

2021 Adherensjunctions______________________.
(a)
canbeusedtobendepithelialsheetsintotubes
(b)
aremostoftenfoundatthebasalsurfaceofcells
(c)
arefoundonlyinadulttissues
(d)
involvefibronectinandintegrininteractions
2022 Atdesmosomes,cadherinmoleculesareconnectedto________________.
(a)
actinfilaments
(b)
intermediatefilaments
(c)
microtubules
(d)
gapjunctions
2023 Hemidesmosomesareimportantfor______________________.
(a)
tubulationofepithelialsheets
(b)
linkagestoglycosaminoglycans
(c)
formingthebasallamina
(d)
attachingepithelialcellstotheextracellularmatrix
2024 Whichofthefollowingstatementsaboutgapjunctionsisfalse?
(a)
Gapjunctionsaremadeofconnexons.
(b)
Moleculesupto1000daltonsinmolecularweightcanmoveacrossgap
junctions.
(c)
Becausegapjunctionsdonotallowionstopassthrough,theyarenotused
forelectricallycouplingcells.
(d)
Gapjunctionscancloseinresponsetoextracellularsignals.
2025 Whichtypeofjunctioninvolvesaconnectiontotheactincytoskeleton?
(a)
adherensjunctions
(b)
desmosomes
(c)
tightjunctions
(d)
gapjunctions
2026 Whichtypeofjunctioncontributesthemosttothepolarizationofepithelialcells?
(a)
adherensjunctions
(b)
desmosomes
(c)
tightjunctions
(d)
gapjunctions
2027 Cadherins______________________.
(a)
areusedtotransferproteinsfromonecelltoanother
(b)
mediatecellcellattachmentsthroughhomophilicinteractions

(c)
(d)

areabundantintheplantcellwall
bindtocollagenfibrils

2028 Plasmodesmata______________________.
(a)
permitsmallmoleculestopassfromonecelltoanother
(b)
arefoundonlyinanimalcells
(c)
areclosedbytheneurotransmitterdopamine
(d)
providetensilestrength

Tissue Maintenance and Renewal


2029 Matchtheappropriatecelltypefoundinthemammalianskinwiththebest
descriptionofitsfunction.

2030 Namethethreekeymechanismsimportantformaintainingtheorganizationof
cellsintotissues.
2031 Placethefollowinginorderoftheirreplacementtimes,fromshortesttolongest.
A.
epidermal cell
B.
nerve cell
C.
bone matrix
D.
red blood cell
E.
cell lining the gut
2032 Cellsthatareterminallydifferentiated______________________.
(a)
willundergoapoptosiswithinafewdays
(b)
cannolongerundergocelldivision
(c)
areunabletomove
(d)
nolongerproduceRNAs
2033 Anadulthemopoieticstemcellfoundinthebonemarrow
______________________.
(a)
willoccasionallyproduceepidermalcellswhennecessary
(b)
canproduceonlyredbloodcells
(c)
canundergoselfrenewingdivisionsforthelifetimeofahealthyanimal
(d)
willexpressallthesametranscriptionfactorsasthosefoundinan
unfertilizedegg

2034 Mouseembryonicstem(ES)cells______________________.
(a)
canonlybeproducedthroughtherapeuticcloning
(b)
cangiverisetoalltissuesandcelltypesinthebodyexceptgermcells
(c)
canbeimplantedinfostermotherstoproduceclonedcowsandother
animals
(d)
comefromtheinnercellmassofearlyembryos
2035 Howdoreproductivecloningandtherapeuticcloningdiffer?
(a)
TheDNAinthenucleusofcellsproducedfortherapeuticcloningis
geneticallyidenticaltothedonorgenome,whereasincellsproducedfor
reproductivecloningitisnot.
(b)
Reproductivecloningrequiresasupplyoffertilizeddonoreggcells,
whereastherapeuticcloningrequiresunfertilizedeggcells.
(c)
Therapeuticcloningrequiresnucleartransplantation,whereasreproductive
cloningdoesnot.
(d)
Embryosareplacedintofostermothersduringreproductivecloningbut
notduringtherapeuticcloning.
2036 Inducedpluripotentstem(iPS)cells______________________.
(a)
arecreatedbytheexpressionofasetofkeygenesincellsderivedfrom
adulttissuessothatthesecellscandifferentiateintoavarietyofcelltypes
(b)
requireasupplyofdonoreggcells,suchasembryonicstemcells
(c)
candifferentiateintoagreatervarietyofadulttissuesthanembryonicstem
cells
(d)
arecreatedbynucleartransplantation
2037 Astemcelldividesintotwodaughtercells.Oneofthedaughtercellsgoesonto
becomeaterminallydifferentiatedcell.Whatisthetypicalfateoftheother
daughter cell?
2038 YourfriendisapioneerinEScellresearch.Inherresearch,sheusesanEScell
linethatoriginatedfromaninbredstrainoflaboratorymicecalledFG426.She
hasjustfiguredoutmethodsthatallowhertogrowanentireliverfromanEScell
andhassuccessfullygrown10livers.Shedemonstratesthatthenewlygrown
liversarefunctionalbysuccessfullytransplantingoneofthenewliversintoa
FG426laboratorymouse.
Youareparticularlyexcitedaboutthis,becauseyouhaveasickpetmouse,
Squeaky.YouareveryattachedtoSqueaky,asyoufoundhimwhenyouwereout
campinginNewHampshire.Unfortunately,Squeakyhasdevelopedliverdisease
andwillnotlivemuchlongerwithoutalivertransplant.Afteryouseeyourfriend
onTVtalkingabouthernewmethodforgrowingmouselivers,youimmediately
grabyourcellphonetoaskherwhetherSqueakycouldhaveoneofthenewly
grownlivers.Justasyouareabouttodialyourfriend,youremembersomething

youlearnedincellbiologyandrealizethatinstead,youshouldaskyourfriend
aboutpossiblyusingtherapeuticcloningforSqueakysbenefit.
A.
Whydoyouthinkthatoneofthenewlygrownliversmaynotworkin
Squeaky?
B.
Explainwhytherapeuticcloningwouldsolvethisproblem.

Cancer
2039 Amalignanttumorismoredangerousthanabenigntumorbecause
______________________.
(a)
itscellsareproliferatingfaster
(b)
itcausesneighboringcellstomutate
(c)
itscellsattackandphagocytoseneighboringnormaltissuecells
(d)
itscellsinvadeothertissues
2040 Whichofthefollowingstatementsaboutcancerisfalse?
(a)
Virusescausesomecancers.
(b)
Tobaccouseisresponsibleformorethan20%ofallcancerdeaths.
(c)
Amutationinevenasinglecancercriticalgeneissufficienttoconverta
normalcellintoacancercell.
(d)
Chemicalcarcinogenscausecancerbychangingthenucleotidesequence
ofDNA.
2041 Cancerisadiseaseofenhancedproliferationandcellsurvival.DNArepair
mechanisms are normally important for cell survival. When a cell senses DNA
damage, the cell cycle is inhibited until the damage is fixed. Given the importance
of DNA repair mechanisms, how can their failure can lead to the production of
cancer cells with a competitive advantage over normal cells?
2042 Whichofthefollowinggeneticchangescannotconvertaprotooncogeneintoan
oncogene?
(a)
Amutationthatintroducesastopcodonimmediatelyafterthecodonfor
theinitiatormethionine.
(b)
Amutationwithinthecodingsequencethatmakestheproteinhyperactive.
(c)
Anamplificationofthenumberofcopiesoftheprotooncogene,causing
overproductionofthenormalprotein.
(d)
Amutationinthepromoteroftheprotooncogene,causingthenormal
proteintobetranscribedandtranslatedatanabnormallyhighlevel.
2043 Whichofthefollowingstatementsabouttumorsuppressorgenesisfalse?
(a)
Geneamplificationofatumorsuppressorgeneislessdangerousthangene
amplificationofaprotooncogene.
(b)
Cellswithonefunctionalcopyofatumorsuppressorgenewillusually
proliferatefasterthannormalcells.

(c)
(d)

Inactivationoftumorsuppressorgenesleadstoenhancedcellsurvivaland
proliferation.
Individualswithonlyonefunctionalcopyofatumorsuppressorgeneare
morepronetocancerthanindividualswithtwofunctionalcopiesofa
tumorsuppressorgene.

2044 Acertainmutationinthereceptorforepidermalgrowthfactor(EGF)causesthe
mutatedreceptorproteintosendapositivesignalalongtheassociated
intracellularsignalingpathwayevenwhentheEGFligandisnotboundtoit.This
signalleadstoabnormalcellproliferationintheabsenceofgrowthfactor.Onthe
basisofthisinformation,wouldyouclassthegenefortheEGFreceptorasa
tumorsuppressorgeneorapotentialoncogene?Explainyouranswer.
2045 RasisaGTPbindingproteinthatisoftendefectiveincancercells.Asignalfrom
agrowthfactorthroughareceptortyrosinekinaseoftenstimulatesnormalcellsto
divide.Whenthereceptortyrosinekinasebindsthegrowthfactor,Rasis
stimulatedtobindGTP.Rasinturnactivatesproteinsthatpromotecell
proliferation.AcommonmutationincancerouscellscausesRastobehaveas
thoughitwereboundtoGTPallthetime.
A.
Whyisthismutationadvantageoustocancerouscells?
B.
YourfrienddecidesthatthesignalingpathwayinvolvingtheRasprotein
isagoodtargetfordrugdesign,becausetheRasproteinisoftendefective
incancercells.Yourfrienddesignsadrugthatwillturnoffthereceptor
tyrosinekinasebypreventingitfromdimerizing.Doyouthinkthatthis
drugwillaffectcellsthathaveadefectiveRasproteinthatactsasifit
werealwaysboundtoGTP?Whyorwhynot?
2046 PeoplewhoinheritonecopyoftheRb(retinoblastoma)genethatisnormaland
onecopythatismutatedthatis,peoplewhoareheterozygousforRbhavea
greatlyincreasedriskofcancer.
Given this information, do you agree or disagree with the following statement?
Explain your answer.
TheRbmutationmusthaveadominanteffect,whichmeansthatit
mustresultinanincreaseinRbfunction.Thus,Rbinitsmutant
formmustbe
anoncogene.
2047 FigureQ2047
mutationsthatmight
developmentof
Explainwhytheloss
advantageousto

showsasequenceof
underliethe
colorectalcancer.
ofp53is
cancerouscells.

Figure Q20-47
2048 Drugsthatblockthefunctionofoncogenicproteinsholdgreatpromiseinthe
fightagainstcancer.Shouldcancerresearchersalsobeattemptingtodesigndrugs
thatwillinterferewiththeproductsoftumorsuppressorgenes?Explain.
2049 Rbisatumorsuppressorgene;itsnormalfunctionistohelprestraincelldivision.
LossofbothcopiesofRbisacausativefactorinsomekindsofcancer.You
proposetotreatthesecancersbyinjectingthepatientswithaviralvectorthat
carriesacopyoftheRbgeneandhastheabilitytoinfectallthecellsofthebody,
therebyartificiallydrivingexpressionofRbinallthecells,includingthecancer
cells.YourcolleaguesaysNo!You'llsimplykillthepatient,becauseyouwill
haltcelldivisionthroughoutthebody.
A.
Whywouldhaltingcelldivisionthroughoutthebodykillafullgrown
adultperson?
B.
IsyourcolleaguerightinthinkingthatforcedexpressionofRbinevery
cellwillhaltallcelldivision?
2050 In1971,DrJudahFolkmanpublishedtheangiogenichypothesissuggestingthat
atumorcannotgrowbeyond12millimeterswithoutthedevelopment
(angiogenesis)ofnewbloodvesselsthatprovideaccesstooxygenandnutrients.
Duringthe1990s,itwasdiscoveredthatvascularendothelialgrowthfactor
(VEGF)stimulatestheproliferationandmigrationofthecellsthatformblood
vessels,leadingtotheformationofnewbloodvessels.VEGFbindstoreceptor
tyrosinekinases(RTKs)onthecellsurfaceandcausestheRTKstodimerizeand
becomeactive,therebyinitiatinganintracellularsignalingcascadethatstimulates
celldivisionandinhibitsapoptosis.Manycancercellssecretehighlevelsof
VEGF.IncreasedVEGFexpressioninatumoriscorrelatedwithapoormedical
outcomeforthepatient.SomeevidencesuggeststhatblockingVEGFdependent
signalingmaypreventtheformationofnewbloodvesselsandleadtothedeathof

immaturebloodvesselswithoutdisturbingmaturebloodvessels.Youworkfora
biotechnologycompanythatseekstocreateanticancerdrugsthatpreventthe
growthoftumorsand/orcausetumorstoshrink,whileleavingnormalcells
relativelyuntouched.AfterlearningaboutVEGF,youhaveabrightideafora
newmechanismofactionforapotentialanticancerdrug.Whatisyouridea?

How We Know: Making Sense of the Genes that Are Critical for
Cancer
2051 YourstudiesincellbiologyhaverevealedhowAPC,aproteinencodedbya
tumorsuppressorgenethatisfrequentlyinactivatedinpeoplewithcolorectal
cancer,functionsintheWntsignalingpathway(seeFigureQ2051).Thishas
inspiredyoutostudyWntsignaling.Youwouldliketodesignadrugtotreat
peoplewithcolorectalcancer.GiventhepathwayshowninFigureQ2051and
theknowledgethatmosthumancolorectaltumorsharbormutationsintheAPC
gene,nameaproteinfromthepathwaythatwouldbeagoodtargetforanactivity
blockinganticancerdrug.Explainyouranswer.

Figure Q20-51

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