title: Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment.
abstract: Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 3' endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes.
authors.affiliation: FRE3377, Institut de Biologie et de Technologies de Saclay (iBiTec-S), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), F-91191 Gif-sur-Yvette cedex, France;
authors.forename: Fanny
authors.initials: F
authors.lastname: Eyboulet
authors.forename: Camille
authors.initials: C
authors.lastname: Cibot
authors.forename: Thomas
authors.initials: T
authors.lastname: Eychenne
authors.forename: Helen
authors.initials: H
authors.lastname: Neil
authors.forename: Olivier
authors.initials: O
authors.lastname: Alibert
authors.forename: Michel
authors.initials: M
authors.lastname: Werner
authors.forename: Julie
authors.initials: J
authors.lastname: Soutourina
mesh_terms: D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D016678:Genome; D006801:Humans; D056892:Mediator Complex / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011836:Radiation Tolerance / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D056892:Mediator Complex; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C082148:SRB4 protein, S cerevisiae; C073998:RAD2 protein, S cerevisiae
keywords: DNA repair; Mediator; RNA polymerase II; Rad2/XPG; Saccharomyces cerevisiae; transcription