第七十章 智云罹难（三）

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    搜：\免费看精品文学sister-chroidcohesionisessentialforproperchroosegregationandfaithfultranssion

    ofthegenoduringthecellcycle.failuretoestab-

    lishorresolvecohesioninatiynerleadstogenoinstabilityandaneuploidy.sister-chro-

    idcohesionisiatedbycohesin，aring-shapedatpasehinethatconsistsofsa，

    s，rad21，andeitherstag1orstag2inhusoiccells.cohesinringstopologicallyentrapdnatogeneratephysicallinkages

    betweensisterchroidsandenablecohesion.cohesinregulatesotherchroobasedpro-

    cesses，suchasdnarepair，transcription，andchroofolding.theseotherfunctionsofcohesinlikelyalsoinvolvethetopologicalentrap-

    tofchrooorpossiblytheextrusionofdnaloops.

    cohesinisloadedontochroointelophaseandg1bythescc2/4plex.beforednareplication，thechrooboundcohesinisdynaand

    isactivelyreedfrohroobythecohesin-releasingfactorwaplwiththehelpofthescaffoldingproteinpds5aorpds5b.duringdnareplication

    insphase，apoolofcohesinisconvertedtothecohesiveforwhichstablyassociateswithchro

    soandiatessister-chroidcohesion.inhu

    cells，cohesionestablishtrequirestheacetylationofsbytheacetyltransferasesesco1and

    esco2andsubsequentrecruittofsororin，whichantagonizeswapltostabilizecohesinon

    chroo.

    thecheckpointkinaseproteins1andrad53arerequiredin

    thebuddingyeast，saccharoescerevisiae，tontaincell

    viabilityinthepresenceofdrugscausingdaetodnaor

    arrestofdnareplicationforks1±3.itisthoughtthattheyactby

    inhibitingcellcycleprogression，allowingtifordnarepairto

    takeplace.1andrad53alsoslowsphaseprogressionin

    responsetodnaalkylation4，althoughthehanisorthis

    anditsrelativeirtanceinprotectingcellsfronadae

    eweshowthatthedna-alkylating

    agenthylhanesulphonateprofoundlyreducesthe

    rateofdnareplicationforkprogreshowever，thiseration

    doesnotrequirerad53or1.theacceleratedsphasein

    checkpointants4，therefore，ispriilyaconsequenceof

    inappropriateinitiationevents5±d-typecellsultielyplete

    dnareplicationinthepresenceof.incontrast，

    replicationforksincheckpointantscollapseirreversiblyat

    highrates.eover，thecytotoxicityofincheckpoint

    antsoccursspecicallywhencellsareallowedtoenters

    phasewithdnadae.thus，preventingdae-induced

    dnareplicationforkcatastropheseetobeapriyhanism

    bywhichcheckpointspreserveviabilityinthefaceofdna

    toensurethatapletesetoftheeukaryoticgenois

    preciselyduplicatedduringtheliedperiodofsphasein

    everycellcycle，dnareplicationinitiatesatanurof

    replicationoriginsonchroo.aseachchrooregionreplicatesina

    specificperiodwithinsphase，tigoforiginactivation

    tberegulated.althoughwehaveagrowingunderstanding

    ofproteinfactorsinvolvedininitiationandelongationof