Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification 英文参考文献.docVIP

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Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification 英文参考文献.doc

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Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification 英文参考文献

ElongatorComplexInfluencesTelomericGeneSilencing andDNADamageResponsebyItsRoleinWobble UridinetRNAModification ChangchunChen1,BoHuang1,2,MattiasEliasson3,4,PatrikRyde′n4,5,AndersS.Bystro¨m1* 1DepartmentofMolecularBiology,Umea?University,Umea?,Sweden,2DivisionofEpidemiology,DepartmentofMedicineandPublicHealth,VanderbiltUniversitySchool ofMedicine,Nashville,Tennessee,UnitedStatesofAmerica,3DepartmentofChemistry,Umea? University,Umea?, Sweden,4ComputationalLifeScienceCluster(CLiC), Umea? University,Umea?, Sweden,5DepartmentofMathematicsandMathematicalStatistics,Umea? University,Umea?, Sweden Abstract Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5- carbamoylmethyluridine (ncm5U34), 5-methoxycarbonylmethyluridine (mcm5U34), and 5-methoxycarbonylmethyl-2-thiour- 5 2 idine (mcm s U34) at wobble position in tRNA. These modified nucleosides are important for efficient decoding during translation.Inarecentpublication,ElongatorcomplexwasimplicatedtoparticipateintelomericgenesilencingandDNA damage response by interacting with proliferating cell nuclear antigen (PCNA). Here we show that elevated levels of , and tRNA UUC, which in a wild-type background contain the mcm5s2U nucleoside at position 34, Glu UUG s 2 suppressthedefectsintelomericgenesilencingandDNAdamageresponseobservedintheElongatormutants.Wealso foundthatthereporteddifferencesintelomericgenesilencingandDNAdamageresponseofvariouselp3allelescorrelated with the levels of modified nucleosides at U34. Defects in telomeric gene silencing and DNA damage response are also Lys Gln tRNA , tRNA s 2 UUU s 2 5 2 observedinstrainswiththetuc2Dmutation,whichabolishtheformationofthe2-thiogroupofthemcm s Unucleosidein Lys tRNA UUU, tRNAGln UUG, and tRNAGlu . These observations show that Elongator complex does not directly mcm 5 s 2 mcm 5 s 2 mcm 5 s 2 UUC participate in telomeric gene silencing and DNA damage response, but rather that modified