Genome-Wide Functional Profiling Identifies Genes and Processes Important for Zinc-Limited Growth of Saccharomyces cerevisiae 英文参考文献.docVIP

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Genome-Wide Functional Profiling Identifies Genes and Processes Important for Zinc-Limited Growth of Saccharomyces cerevisiae 英文参考文献.doc

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Genome-Wide Functional Profiling Identifies Genes and Processes Important for Zinc-Limited Growth of Saccharomyces cerevisiae 英文参考文献

Genome-WideFunctionalProfilingIdentifiesGenesand ProcessesImportantforZinc-LimitedGrowthof Saccharomycescerevisiae MatthewNorth1.,JanetSteffen2.,AlexV.Loguinov1,GinelleR.Zimmerman2,ChrisD.Vulpe1, DavidJ.Eide2* 1DepartmentofNutritionalScienceandToxicology,UniversityofCaliforniaBerkeley,Berkeley,California,UnitedStatesofAmerica,2DepartmentofNutritionalSciences, UniversityofWisconsin–Madison,Madison,Wisconsin,UnitedStatesofAmerica Abstract Zincisanessentialnutrientbecauseitisarequiredcofactorformanyenzymesandtranscriptionfactors.Todiscovergenesand processesinyeastthatarerequiredforgrowthwhenzincislimiting,weusedgenome-widefunctionalprofiling.Mixedpools of,4,600deletionmutantswereinoculatedintozinc-repleteandzinc-limitingmedia.Thesecellsweregrownforseveral generations,andtheprevalenceofeachmutantinthepool wasthendeterminedbymicroarrayanalysis.Asaresult,we identified more than 400 different genes required for optimal growth under zinc-limiting conditions. Among these were severaltargetsoftheZap1zinc-responsivetranscriptionfactor.Theirimportanceisconsistentwiththeirup-regulationbyZap1 inlowzinc.WealsoidentifiedgenesthatimplicateZap1-independentprocessesasimportant.Theseincludeendoplasmic reticulumfunction,oxidativestressresistance,vesiculartrafficking,peroxisomebiogenesis,andchromatinmodification.Our studiesalsoindicatedthecriticalroleofmacroautophagyinlowzincgrowth.Finally,asaresultofouranalysis,wediscovereda previouslyunknownrolefortheICE2geneinmaintainingERzinchomeostasis.Thus,functionalprofilinghasprovidedmany newinsightsintogenesandprocessesthatareneededforcellstothriveunderthestressofzincdeficiency. Citation:NorthM,SteffenJ,LoguinovAV,ZimmermanGR,VulpeCD,etal.(2012)Genome-WideFunctionalProfilingIdentifiesGenesandProcessesImportant forZinc-LimitedGrowthofSaccharomycescerevisiae.PLoSGenet8(6):e1002699.doi:10.1371/journal.pgen.1002699 Editor:CarolineC.Philpott,NationalInstituteofDiabetesandDigestiveandKidneyDiseases,UnitedStatesofAmerica ReceivedJanuary16,2012;A