title: Genome-wide analysis of factors affecting transcription elongation and DNA repair: a new role for PAF and Ccr4-not in transcription-coupled repair.
abstract: RNA polymerases frequently deal with a number of obstacles during transcription elongation that need to be removed for transcription resumption. One important type of hindrance consists of DNA lesions, which are removed by transcription-coupled repair (TC-NER), a specific sub-pathway of nucleotide excision repair. To improve our knowledge of transcription elongation and its coupling to TC-NER, we used the yeast library of non-essential knock-out mutations to screen for genes conferring resistance to the transcription-elongation inhibitor mycophenolic acid and the DNA-damaging agent 4-nitroquinoline-N-oxide. Our data provide evidence that subunits of the SAGA and Ccr4-Not complexes, Mediator, Bre1, Bur2, and Fun12 affect transcription elongation to different extents. Given the dependency of TC-NER on RNA Polymerase II transcription and the fact that the few proteins known to be involved in TC-NER are related to transcription, we performed 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, unraveling a novel function for these transcription complexes and opening new perspectives for the understanding of TC-NER and its functional interconnection with transcription elongation.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Sevilla, Spain.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gaillard
authors.forename: Cristina
authors.initials: C
authors.lastname: Tous
authors.forename: Javier
authors.initials: J
authors.lastname: Botet
authors.forename: Cristina
authors.initials: C
authors.lastname: González-Aguilera
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Quintero
authors.forename: Laia
authors.initials: L
authors.lastname: Viladevall
authors.forename: María L
authors.initials: ML
authors.lastname: García-Rubio
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rodríguez-Gil
authors.forename: Antonio
authors.initials: A
authors.lastname: Marín
authors.forename: Joaquín
authors.initials: J
authors.lastname: Ariño
authors.forename: José Luis
authors.initials: JL
authors.lastname: Revuelta
authors.forename: Sebastián
authors.initials: S
authors.lastname: Chávez
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
mesh_terms: D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism
chemical_list: C472168:Bre1 protein, S cerevisiae; D004271:DNA, Fungal; D015852:Eukaryotic Initiation Factor-2; C451460:FUN12 protein, S cerevisiae; D012333:RNA, Messenger; C507785:SAGA complex, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; C086603:Matk protein, mouse; D016392:Proto-Oncogene Proteins pp60(c-src); C078657:CCR4 protein, S cerevisiae; D012260:Ribonucleases; D045643:DNA Repair Enzymes