FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1 英文参考文献.docVIP

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FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1 英文参考文献.doc

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FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1 英文参考文献

FACTPreventstheAccumulationofFreeHistones EvictedfromTranscribedChromatinandaSubsequent CellCycleDelayinG1 MacarenaMorillo-Huesca1.,DouglasMaya1.,MariCruzMun?oz-Centeno1*,RakeshKumarSingh2, VincentOreal3,GajjalaiahvariUganderReddy2,DunLiang2,VincentGe′li3,AkashGunjan2,Sebastia′n Cha′vez1* 1DepartamentodeGene′tica,UniversidaddeSevilla,Seville,Spain,2DepartmentofBiomedicalSciences,CollegeofMedicine,FloridaStateUniversity,Tallahassee,Florida, United States of America, 3Laboratoire d’Instabilite′ Ge′ne′tique et Cance′rogene`se, Institut de Biologie Struturale et Microbiologie, Centre National de la Recherche Scientifique,Marseille,France Abstract TheFACTcomplexparticipatesinchromatinassemblyanddisassemblyduringtranscriptionelongation.Theyeastmutants affectedintheSPT16gene,whichencodesoneoftheFACTsubunits,altertheexpressionofG1cyclinsandexhibitdefects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down- regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3) in START by specifically triggeringtherepressionofitspromoter.TheG1delayundergonebyspt16mutantsisnotmediatedbytheDNA–damage checkpoint,althoughthemutationofRAD53,whichisotherwiseinvolvedinhistonedegradation,enhancesthecell-cycle defectsofspt16-197.WerevealhowFACTdysfunctiontriggersanaccumulationoffreehistonesevictedfromtranscribed chromatin.Thisaccumulationisenhancedinarad53backgroundandleadstoadelayinG1.Consistently,weshowthatthe overexpressionofhistonesinwild-typecellsdown-regulatesCLN3inSTARTandcausesadelayinG1.Ourworkshowsthat chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatinanddescribesanewcellcyclephenomenonthatallowscellstorespondtoexcesshistonesbeforestartingDNA replication. Citation: Morillo-Huesca M, Maya D, Mun?oz-Centeno MC, Singh RK, Oreal V, et al. (2010) FACT Prevents the Accumulation of Free Histones Evicted from Transcr