Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair 英文参考文献.docVIP

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Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair 英文参考文献.doc

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Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair 英文参考文献

Genome-WideAnalysisofFactorsAffectingTranscription ElongationandDNARepair:ANewRoleforPAFand Ccr4-NotinTranscription-CoupledRepair He′le`neGaillard1,2,CristinaTous1,2,JavierBotet3,CristinaGonza′lez-Aguilera1,2,MariaJose′ Quintero2, LaiaViladevall4,Mar?′aL.Garc?′a-Rubio1,2,AlfonsoRodr?′guez-Gil2,AntonioMar?′n2,Joaqu?′nArin?o4,Jose′ LuisRevuelta3,Sebastia′nCha′vez2,Andre′sAguilera1,2* 1Centro Andaluz de Biolog?′a Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Sevilla, Spain, 2Departamento de Gene′tica, F. Biolog?′a, UniversidaddeSevilla,Sevilla,Spain,3InstitutodeMicrobiolog?′aBioqu?′mica,UniversidaddeSalamanca-CSIC,Salamanca,Spain,4DepartamentodeBioqu?′micayBiolog?′a Molecular,F.Veterinaria,UniversitatAuto′nomaBarcelona,Barcelona,Spain Abstract RNApolymerasesfrequentlydealwithanumberofobstaclesduringtranscriptionelongationthatneedtoberemovedfor transcriptionresumption.OneimportanttypeofhindranceconsistsofDNAlesions,whichareremovedbytranscription- coupledrepair(TC-NER),aspecificsub-pathwayofnucleotideexcisionrepair.Toimproveourknowledgeoftranscription elongationanditscouplingtoTC-NER,weusedtheyeastlibraryofnon-essentialknock-outmutationstoscreenforgenes conferring resistance to the transcription-elongation inhibitor mycophenolic acid and the DNA-damaging agent 4- nitroquinoline-N-oxide.OurdataprovideevidencethatsubunitsoftheSAGAandCcr4-Notcomplexes,Mediator,Bre1,Bur2, and Fun12 affect transcription elongation to different extents. Given the dependency of TC-NER on RNA Polymerase II transcriptionandthefactthatthefewproteinsknowntobeinvolvedinTC-NERarerelatedtotranscription,weperformed an in-depth TC-NER analysis of a selection of mutants. We found that mutants of the PAF and Ccr4-Not complexes are impaired in TC-NER. This study provides evidence that PAF and Ccr4-Not are required for efficient TC-NER in yeast, unravelinganovelfunctionforthesetranscriptioncomplexesandopeningnewperspectivesfortheunderstandingofTC- NERanditsfunctionalinterco