title: In vivo interactions of TTDA mutant proteins within TFIIH.
abstract: Trichothiodystrophy group A (TTD-A) patients carry a mutation in the transcription factor II H (TFIIH) subunit TTDA. Using a novel in vivo tripartite split-GFP system, we show that TTDA interacts with the TFIIH subunit p52 and the p52-TTDA-GFP product is incorporated into TFIIH. p52-TTDA-GFP is able to bind DNA and is recruited to UV-damaged DNA. Furthermore, we show that two patient-mutated TTDA proteins can interact with p52, are able to bind to the DNA and can localize to damaged DNA. Our findings give new insights into the behavior of TTDA within the context of a living cell and thereby shed light on the complex phenotype of TTD-A patients.
authors.affiliation: CNRS, IPBS, 205 route de Narbonne, 31077 Toulouse, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Nonnekens
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cabantous
authors.forename: Joris
authors.initials: J
authors.lastname: Slingerland
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Mari
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Giglia-Mari
mesh_terms: D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D005347:Fibroblasts; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D051758:Transcription Factor TFIIH / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D054463:Trichothiodystrophy Syndromes / Q000235:genetics* / Q000378:metabolism*
chemical_list: C512380:GTF2H5 protein, human; D050505:Mutant Proteins; D021122:Protein Subunits; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D004247:DNA
keywords: Protein–protein interactions; TFIIH; TTDA; Trichothiodystrophy; Tripartite split-GFP