title: XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients.
abstract: Mutations in the human XPG gene give rise to an inherited photosensitive disorder, xeroderma pigmentosum (XP) associated with Cockayne syndrome (XP-G/CS). The clinical features of CS in XP-G/CS patients are difficult to explain on the basis of a defect in nucleotide excision repair (NER). We found that XPG forms a stable complex with TFIIH, which is active in transcription and NER. Mutations in XPG found in XP-G/CS patient cells that prevent the association with TFIIH also resulted in the dissociation of CAK and XPD from the core TFIIH. As a consequence, the phosphorylation and transactivation of nuclear receptors were disturbed in XP-G/CS as well as xpg(-/-) MEF cells and could be restored by expression of wild-type XPG. These results provide an insight into the role of XPG in the stabilization of TFIIH and the regulation of gene expression and provide an explanation of some of the clinical features of XP-G/CS.
authors.affiliation: Laboratories for Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ito
authors.forename: Isao
authors.initials: I
authors.lastname: Kuraoka
authors.forename: Pierre
authors.initials: P
authors.lastname: Chymkowitch
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Compe
authors.forename: Arato
authors.initials: A
authors.lastname: Takedachi
authors.forename: Chie
authors.initials: C
authors.lastname: Ishigami
authors.forename: Frédéric
authors.initials: F
authors.lastname: Coin
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Egly
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D003057:Cockayne Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004355:Drug Stability; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D000095043:Cyclin-Dependent Kinase-Activating Kinase; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D018844:Cyclin-Dependent Kinases; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D000095043:Cyclin-Dependent Kinase-Activating Kinase; D000099250:DNA Excision Repair Protein ERCC-5