Shelterin-Like Proteins and Yku Inhibit Nucleolytic Processing of Saccharomyces cerevisiae Telomeres 英文参考文献.docVIP

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Shelterin-Like Proteins and Yku Inhibit Nucleolytic Processing of Saccharomyces cerevisiae Telomeres 英文参考文献.doc

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Shelterin-Like Proteins and Yku Inhibit Nucleolytic Processing of Saccharomyces cerevisiae Telomeres 英文参考文献

Shelterin-LikeProteinsandYkuInhibitNucleolytic ProcessingofSaccharomycescerevisiaeTelomeres DiegoBonetti,MichelaClerici,SavaniAnbalagan,MarinaMartina,GiovannaLucchini,MariaPia Longhese* DipartimentodiBiotecnologieeBioscienze,Universita` diMilano-Bicocca,Milano,Italy Abstract EukaryoticcellsdistinguishtheirchromosomeendsfromaccidentalDNAdouble-strandbreaks(DSBs)bypackagingthem intoprotectivestructurescalledtelomeresthatpreventDNArepair/recombinationactivities.Hereweinvestigatetheroleof keytelomericproteinsinprotectingbuddingyeasttelomeresfromdegradation.WeshowthattheSaccharomycescerevisiae shelterin-likeproteinsRif1,Rif2,andRap1inhibitnucleolyticprocessingatbothdenovoandnativetelomeresduringG1 andG2cellcyclephases,withRif2andRap1showingthestrongesteffects.AlsoYkupreventstelomereresectioninG1, independently of its role in non-homologous end joining. Yku and the shelterin-like proteins have additive effects in inhibitingDNAdegradationatG1denovotelomeres,whereYkuplaysthemajorroleinpreventinginitiation,whereasRif1, Rif2, andRap1 act primarily by limiting extensive resection. Infact, exonucleolytic degradation ofade novo telomereis moreefficientinyku70Dthaninrif2DG1cells,butgenerationofssDNAinYku-lackingcellsislimitedtoDNAregionsclose tothetelomeretip.ThislimitedprocessingisduetotheinhibitoryactionofRap1,Rif1,andRif2,astheirinactivationallows extensive telomere resection not only in wild-type but also in yku70D G1 cells. Finally, Rap1 and Rif2 prevent telomere degradation by inhibiting MRX access to telomeres, which are also protected from the Exo1 nuclease by Yku. Thus, chromosomeenddegradationiscontrolledbytelomericproteinsthatspecificallyinhibittheactionofdifferentnucleases. Citation:BonettiD,ClericiM,AnbalaganS,MartinaM,LucchiniG,etal.(2010)Shelterin-LikeProteinsandYkuInhibitNucleolyticProcessingofSaccharomyces cerevisiaeTelomeres.PLoSGenet6(5):e1000966.doi:10.1371/journal.pgen.1000966 Editor:JamesE.Haber,BrandeisUniversity,UnitedStatesofAmerica ReceivedFebruary16