Emergence of Micronuclei and Their Effects on the Fate of Cells under Replication Stress 英文参考文献.docVIP

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Emergence of Micronuclei and Their Effects on the Fate of Cells under Replication Stress 英文参考文献.doc

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Emergence of Micronuclei and Their Effects on the Fate of Cells under Replication Stress 英文参考文献

EmergenceofMicronucleiandTheirEffectsontheFate ofCellsunderReplicationStress Koh-ichiUtani,YukaKohno,AtsushiOkamoto,NoriakiShimizu* GraduateSchoolofBiosphereScience,HiroshimaUniversity,Hiroshima,Japan Abstract The presence of micronuclei in mammalian cells is related to several mutagenetic stresses. In order to understand how micronucleiemerge,behaveincells,andaffectcellfate,weperformedextensivetime-lapsemicroscopyofHeLaH2B-GFPcells inthepresenceofhydroxyureaatlowconcentration.Micronucleiformedaftermitosisfromlaggingchromatidsorchromatin bridgesbetweenanaphasechromosomesandwerestablymaintainedinthecellsforuptoonecellcycle.Nuclearbudsalso formedfromchromatinbridgesorduringinterphase.Ifthemicronuclei-bearingcellsenteredmitosis,theyeitherproduced daughtercellswithoutmicronucleior,morefrequently,producedcellswithadditionalmicronuclei.Lowconcentrationsof hydroxyurea efficiently induced multipolar mitosis, which generated lagging chromatids or chromatin bridges, and also generatedmultinuclearcellsthatweretightlylinkedtoapoptosis.Wefoundthatthepresenceofmicronucleiisrelatedto apoptosis but not to multipolar mitosis. Furthermore, the structural heterogeneity among micronuclei, with respect to chromatin condensation or the presence of lamin B, derived from the mechanism of micronuclei formation. Our study reinforcesthenotionthatmicronucleationhasimportantimplicationsinthegenomicplasticityoftumorcells. Citation: Utani K-i, Kohno Y, Okamoto A, Shimizu N (2010) Emergence of Micronuclei and Their Effects on the Fate of Cells under Replication Stress. PLoS ONE5(4):e10089.doi:10.1371/journal.pone.0010089 Editor:MichaelFreitag,OregonStateUniversity,UnitedStatesofAmerica ReceivedFebruary23,2010;AcceptedMarch16,2010;PublishedApril8,2010 Copyright: ? 2010 Utani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredite