Multiple Means to the Same End The Genetic Basis of Acquired Stress Resistance in Yeast 英文参考文献.docVIP

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Multiple Means to the Same End The Genetic Basis of Acquired Stress Resistance in Yeast 英文参考文献.doc

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Multiple Means to the Same End The Genetic Basis of Acquired Stress Resistance in Yeast 英文参考文献

MultipleMeanstotheSameEnd:TheGeneticBasisof AcquiredStressResistanceinYeast DavidB.Berry1,QiaoningGuan1¤,JamesHose1,SuraiyaHaroon1,MarinellaGebbia2,3,LawrenceE. Heisler2,3,CoreyNislow2,4,GuriGiaever2,3,AudreyP.Gasch1,5 * 1Laboratory of Genetics, University of Wisconsin–Madison, Madison, Wisconsin, United States of America, 2Terrance Donnelly Centre for Cellular and Biomolecular Research, Toronto, Canada, 3Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada, 4Banting and Best Department of Medical Research, UniversityofToronto,Toronto,Canada,5GenomeCenterofWisconsin,UniversityofWisconsin–Madison,Madison,Wisconsin,UnitedStatesofAmerica Abstract In nature, stressful environments often occur in combination or close succession, and thus the ability to prepare for impendingstresslikelyprovidesasignificantfitnessadvantage.Organismsexposedtoamilddoseofstresscanbecome toleranttowhatwouldotherwisebealethaldoseofsubsequentstress;however,themechanismofthisacquiredstress toleranceispoorlyunderstood.Toexplorethis,weexposedtheyeastgene-deletionlibraries,whichinterrogateallessential and non-essential genes, to successive stress treatments and identified genes necessary for acquiring subsequent stress resistance. Cells were exposed to one of three different mild stress pretreatments (salt, DTT, or heat shock) and then challengedwithaseveredoseofhydrogenperoxide(H2O2).Surprisingly,therewaslittleoverlapinthegenesrequiredfor acquisitionofH2O2toleranceafterdifferentmild-stresspretreatments,revealingdistinctmechanismsofsurvivingH2O2in each case. Integrative network analysis of these results with respect to protein–protein interactions, synthetic–genetic interactions,andfunctionalannotationsidentifiedmanyprocessesnotpreviouslylinkedtoH2O2tolerance.Wetestedand present several models that explain the lack of overlap in genes required for H2O2 tolerance after each of the three pretreatments.Together,thisworkshowsthatacquiredtolerancetothesameseverestressoccursbydi