Recruitment of Rad51 and Rad52 to Short Telomeres Triggers a Mec1-Mediated Hypersensitivity to Double-Stranded DNA Breaks in Senescent Budding Yeast 英文参考文献.docVIP

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Recruitment of Rad51 and Rad52 to Short Telomeres Triggers a Mec1-Mediated Hypersensitivity to Double-Stranded DNA Breaks in Senescent Budding Yeast 英文参考文献.doc

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Recruitment of Rad51 and Rad52 to Short Telomeres Triggers a Mec1-Mediated Hypersensitivity to Double-Stranded DNA Breaks in Senescent Budding Yeast 英文参考文献

RecruitmentofRad51andRad52toShortTelomeres TriggersaMec1-MediatedHypersensitivitytoDouble- StrandedDNABreaksinSenescentBuddingYeast Yi-HsuanLin,Chia-ChingChang,Chui-WeiWong,Shu-ChunTeng* DepartmentofMicrobiology,CollegeofMedicine,NationalTaiwanUniversity,Taipei,Taiwan Abstract Telomere maintenance is required for chromosome stability, and telomeres are typically replicated by the action of telomerase. In both mammalian tumor and yeast cells that lack telomerase, telomeres are maintained by an alternative recombinationmechanism.HerewedemonstratedthatthebuddingyeastSaccharomycescerevisiaetypeIsurvivorsderived fromtelomerase-deficientcellswerehypersensitivetoDNAdamagingagents.Assaystotracktelomerelengthsanddrug sensitivity of telomerase-deficient cells from spore colonies to survivors suggested a correlation between telomere shortening and bleomycin sensitivity. Our genetic studies demonstrated that this sensitivity depends on Mec1, which signals checkpoint activation, leading to prolonged cell-cycle arrest in senescent budding yeasts. Moreover, we also observedthatwhencellsequippedwithshorttelomeres,recruitmentsofhomologousrecombinationproteins,Rad51and Rad52,werereducedatanHO-endonuclease-catalyzeddouble-strandbreak(DSB),whiletheirassociationswereincreased atchromosomeends.Theseresultssuggestedthatthesensitivephenotypemaybeattributedtothesequestrationofrepair proteinstocompromisedtelomeres,thuslimitingtherepaircapacityatbonafideDSBsites. Citation:LinY-H,ChangC-C,WongC-W,TengS-C(2009)RecruitmentofRad51andRad52toShortTelomeresTriggersaMec1-MediatedHypersensitivityto Double-StrandedDNABreaksinSenescentBuddingYeast.PLoSONE4(12):e8224.doi:10.1371/journal.pone.0008224 Editor:MichaelPolymenis,TexasAMUniversity,UnitedStatesofAmerica ReceivedOctober17,2009;AcceptedNovember16,2009;PublishedDecember14,2009 Copyright:?2009Linetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductionina