Nonredundant Requirement for Multiple Histone Modifications for the Early Anaphase Release of the Mitotic Exit Regulator Cdc14 from Nucleolar Chromatin 英文参考文献.docVIP

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Nonredundant Requirement for Multiple Histone Modifications for the Early Anaphase Release of the Mitotic Exit Regulator Cdc14 from Nucleolar Chromatin 英文参考文献.doc

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Nonredundant Requirement for Multiple Histone Modifications for the Early Anaphase Release of the Mitotic Exit Regulator Cdc14 from Nucleolar Chromatin 英文参考文献

NonredundantRequirementforMultipleHistone ModificationsfortheEarlyAnaphaseReleaseofthe MitoticExitRegulatorCdc14fromNucleolarChromatin WilliamW.Hwang,HitenD.Madhani* DepartmentofBiochemistryandBiophysics,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica Abstract In Saccharomyces cerevisiae, the conserved phosphatase Cdc14 is required for the exit from mitosis. It is anchored on nucleolarchromatinbytheCfi1/Net1proteinuntilearlyanaphase,atwhichtimeitisreleasedintothenucleoplasm.Two poorly understood, redundant pathways promote Cdc14 release, the FEAR (Cdc fourteen early release) network and the MEN (mitotic exit network). Through the analysis of genetic interactions, we report here a novel requirement for the ubiquitination of histone H2B by the Bre1 ubiquitin ligase in the cell cycle–dependent release of Cdc14 from nucleolar chromatinwhen theMEN is inactivated.This functionforH2B ubiquitinationis mediated by itsactivation of histoneH3 methylationonlysines4 and79(meH3K4andmeH3K79)but, surprisingly, isnotdependentonthehistonedeacetylase (HDAC)Sir2,whichassociateswithCdc14onnucleolarchromatinaspartoftheRENTcomplex.Wealsoobservedadefectin Cdc14 release in cells lacking H3 lysine 36 methylation (meH3K36) and in cells lacking an HDAC recruited by this modification.Thesehistonemodificationsrepresentpreviouslyunappreciatedfactorsrequiredfortheaccessibilitytoand/or actiononnucleolarchromatinofFEARnetworkcomponents.Thenonredundantroleforthesemodificationsinthiscontext contrastswiththenotionofahighlycombinatorialcodebywhichhistonemarksacttocontrolbiologicalprocesses. Citation: Hwang WW, Madhani HD (2009) Nonredundant Requirement for Multiple Histone Modifications for the Early Anaphase Release of the Mitotic Exit RegulatorCdc14fromNucleolarChromatin.PLoSGenet5(8):e1000588.doi:10.1371/journal.pgen.1000588 Editor:AsifaAkhtar,EuropeanMolecularBiologyLaboratory,Germany ReceivedNovember20,2008;AcceptedJuly7,2009;PublishedAugust7,2009 Copyright:?20