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Cdk2 Is Required for p53-Independent G2M Checkpoint Control 英文参考文献
Cdk2IsRequiredforp53-IndependentG2/MCheckpoint
Control
JonH.Chung,FredBunz*
Department of Radiation Oncology and Molecular Radiation Sciences and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of
Medicine,Baltimore,Maryland,UnitedStatesofAmerica
Abstract
Theactivationofphase-specificcyclin-dependentkinases(Cdks)isassociatedwithorderedcellcycletransitions.Amongthe
mammalianCdks,onlyCdk1isessentialforsomaticcellproliferation.Cdk1canapparentlysubstituteforCdk2,Cdk4,and
Cdk6,whichareindividuallydispensableinmice.Itisunclearifallfunctionsofnon-essentialCdksarefullyredundantwith
Cdk1.Usingageneticapproach,weshowthatCdk2,theS-phaseCdk,uniquelycontrolstheG2/Mcheckpointthatprevents
cells with damaged DNA from initiating mitosis. CDK2-nullizygous human cells exposed to ionizing radiation failed to
excludeCdk1fromthenucleusandexhibitedamarkeddefectinG2/MarrestthatwasunmaskedbythedisruptionofP53.
The DNA replication licensing protein Cdc6, which is normally stabilized by Cdk2, was physically associated with the
checkpointregulatorATRandwasrequiredforefficientATR-Chk1-Cdc25Asignaling.ThesefindingsdemonstratethatCdk2
maintainsabalanceofS-phaseregulatoryproteinsandtherebycoordinatessubsequentp53-independentG2/Mcheckpoint
activation.
Citation: Chung JH, Bunz F (2010) Cdk2 Is Required for p53-Independent G2/M Checkpoint Control. PLoS Genet 6(2): e1000863. doi:10.1371/
journal.pgen.1000863
Editor:SueBiggins,FredHutchinsonCancerResearchCenter,UnitedStatesofAmerica
ReceivedSeptember23,2009;AcceptedJanuary28,2010;PublishedFebruary26,2010
Copyright: ? 2010 Chung, Bunz. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:ThisworkwassupportedbytheFlightAttendantMedicalResearchInstitute(FAMRI),ClinicalInnovatorAward();theNationalCancer
Institute(grant#CA104253);andtheW.W.SmithCha
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