title: Regulation of Transcription Elongation by the XPG-TFIIH Complex Is Implicated in Cockayne Syndrome.
abstract: XPG is a causative gene underlying the photosensitive disorder xeroderma pigmentosum group G (XP-G) and is involved in nucleotide excision repair. Here, we show that XPG knockdown represses epidermal growth factor (EGF)-induced FOS transcription at the level of transcription elongation with little effect on EGF signal transduction. XPG interacted with transcription elongation factors in concert with TFIIH, suggesting that the XPG-TFIIH complex serves as a transcription elongation factor. The XPG-TFIIH complex was recruited to promoter and coding regions of both EGF-induced (FOS) and housekeeping (EEF1A1) genes. Further, EGF-induced recruitment of RNA polymerase II and TFIIH to FOS was reduced by XPG knockdown. Importantly, EGF-induced FOS transcription was markedly lower in XP-G/Cockayne syndrome (CS) cells expressing truncated XPG than in control cells expressing wild-type (WT) XPG, with less significant decreases in XP-G cells with XPG nuclease domain mutations. In corroboration of this finding, both WT XPG and a missense XPG mutant from an XP-G patient were recruited to FOS upon EGF stimulation, but an XPG mutant mimicking a C-terminal truncation from an XP-G/CS patient was not. These results suggest that the XPG-TFIIH complex is involved in transcription elongation and that defects in this association may partly account for Cockayne syndrome in XP-G/CS patients.
authors.affiliation: Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan tnarita@fbs.osaka-u.ac.jp ktanaka@fbs.osaka-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Narita
authors.affiliation: Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Narita
authors.affiliation: Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Arato
authors.initials: A
authors.lastname: Takedachi
authors.affiliation: Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Saijo
authors.affiliation: Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan tnarita@fbs.osaka-u.ac.jp ktanaka@fbs.osaka-u.ac.jp.
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D045744:Cell Line, Tumor; D003057:Cockayne Syndrome / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D020648:Peptide Elongation Factor 1 / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D015398:Signal Transduction; D061805:Transcription Elongation, Genetic / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D019474:Transcription Factors, TFIII / Q000378:metabolism*; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D004815:Epidermal Growth Factor; D009687:Nuclear Proteins; D020648:Peptide Elongation Factor 1; D016760:Proto-Oncogene Proteins c-fos; D012319:RNA Polymerase II; D014157:Transcription Factors; D019474:Transcription Factors, TFIII; D000099250:DNA Excision Repair Protein ERCC-5; C094814:EEF1A1 protein, human