Regulation of Septin Dynamics by the Saccharomyces cerevisiae Lysine Acetyltransferase NuA4 英文参考文献.docVIP

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Regulation of Septin Dynamics by the Saccharomyces cerevisiae Lysine Acetyltransferase NuA4 英文参考文献.doc

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Regulation of Septin Dynamics by the Saccharomyces cerevisiae Lysine Acetyltransferase NuA4 英文参考文献

RegulationofSeptinDynamicsbytheSaccharomyces cerevisiaeLysineAcetyltransferaseNuA4 LeslieMitchell,AndreaLau,Jean-PhilippeLambert,HuZhou,YingFong,Jean-Franc?oisCouture,Daniel Figeys,KristinBaetz* OttawaInstituteofSystemsBiology,DepartmentofBiochemistry,Microbiology,andImmunology,UniversityofOttawa,Ottawa,Ontario,Canada Abstract In the budding yeast Saccharomyces cerevisiae, the lysine acetyltransferase NuA4 has been linked to a host of cellular processesthroughtheacetylationofhistoneandnon-histonetargets.TodiscoverproteinsregulatedbyNuA4-dependent acetylation,weperformedgenome-widesyntheticdosagelethalscreenstoidentifygeneswhoseoverexpressionistoxicto non-essential NuA4 deletion mutants. The resulting genetic network identified a novel link between NuA4 and septin proteins,agroupofhighlyconservedGTP-bindingproteinsthatfunctionincytokinesis.Weshowthatacetyltransferase- deficientNuA4mutantshavedefectsinseptincollarformationresultinginthedevelopmentofelongatedbudsthroughthe Swe1-dependent morphogenesis checkpoint. We have discovered multiple sites of acetylation on four of the five yeast mitoticseptins,Cdc3,Cdc10,Cdc12andShs1,anddeterminedthatNuA4canacetylatethreeofthefourinvitro.Invivowe findthatacetylationlevelsofbothShs1andCdc10arereducedinacatalyticallyinactiveesa1mutant.Finally,wedetermine thatcellsexpressingaShs1proteinwithdecreasedacetylationinvivohavedefectsinseptinlocalizationthataresimilarto thoseobservedinNuA4mutants.Thesefindingsprovidethefirstevidencethatyeastseptinproteinsareacetylatedand thatNuA4impactsseptindynamics. Citation:MitchellL,LauA,LambertJ-P,ZhouH,FongY,etal.(2011)RegulationofSeptinDynamicsbytheSaccharomycescerevisiaeLysineAcetyltransferase NuA4.PLoSONE6(10):e25336.doi:10.1371/journal.pone.0025336 Editor:KevinG.Hardwick,UniversityofEdinburgh,UnitedKingdom ReceivedJuly7,2011;AcceptedSeptember1,2011;PublishedOctober3,2011 Copyright: ? 2011 Mitchell et al. This is an open-access article distributed under the terms of the Creative Commons Attribu