title: TFIIH is an elongation factor of RNA polymerase I.
abstract: TFIIH is a multisubunit factor essential for transcription initiation and promoter escape of RNA polymerase II and for the opening of damaged DNA double strands in nucleotide excision repair (NER). In this study, we have analyzed at which step of the transcription cycle TFIIH is essential for transcription by RNA polymerase I. We demonstrate that TFIIH associates with the rDNA promoter and gene-internal sequences and leaves the rDNA promoter in a complex with RNA polymerase I after start of transcription. Moreover, mutations in the TFIIH subunits XPB and XPD found in Cockayne syndrome impair the interaction of TFIIH with the rDNA, but do not influence initiation complex formation or promoter escape of RNA polymerase I, but preclude the productivity of the enzyme by reducing transcription elongation in vivo and in vitro. Our results implicate that reduced RNA polymerase I transcription elongation and ribosomal stress could be one factor contributing to the Cockayne syndrome phenotype.
authors.affiliation: Department of Dermatology and Allergic Diseases, University of Ulm, James-Franck Ring N27, 89081 Ulm, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Assfalg
authors.forename: Anton
authors.initials: A
authors.lastname: Lebedev
authors.forename: Omar Garcia
authors.initials: OG
authors.lastname: Gonzalez
authors.forename: Adrian
authors.initials: A
authors.lastname: Schelling
authors.forename: Sylvia
authors.initials: S
authors.lastname: Koch
authors.forename: Sebastian
authors.initials: S
authors.lastname: Iben
mesh_terms: D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004275:DNA, Ribosomal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I / Q000378:metabolism*; D051758:Transcription Factor TFIIH / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D035602:Transcriptional Elongation Factors; C072022:XPBC-ERCC-3 protein; D051758:Transcription Factor TFIIH; D012318:RNA Polymerase I; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human