title: TFIIH contains a PH domain involved in DNA nucleotide excision repair.
abstract: The human general transcription factor TFIIH is involved in both transcription and DNA repair. We have identified a structural domain in the core subunit of TFIIH, p62, which is absolutely required for DNA repair activity through the nucleotide excision repair pathway. Using coimmunoprecipitation experiments, we showed that this activity involves the interaction between the N-terminal domain of p62 and the 3' endonuclease XPG, a major component of the nucleotide excision repair machinery. Furthermore, we reconstituted a functional TFIIH particle with a mutant of p62 lacking the N-terminal domain, showing that this domain is not required for assembly of the TFIIH complex and basal transcription. We solved its three-dimensional structure and found an unpredicted pleckstrin homology and phosphotyrosine binding (PH/PTB) domain, uncovering a new class of activity for this fold.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Gervais
authors.forename: Valérie
authors.initials: V
authors.lastname: Lamour
authors.forename: Anass
authors.initials: A
authors.lastname: Jawhari
authors.forename: Florent
authors.initials: F
authors.lastname: Frindel
authors.forename: Emeric
authors.initials: E
authors.lastname: Wasielewski
authors.forename: Sandy
authors.initials: S
authors.lastname: Dubaele
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Egly
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Thierry
authors.forename: Bruno
authors.initials: B
authors.lastname: Kieffer
authors.forename: Arnaud
authors.initials: A
authors.lastname: Poterszman
mesh_terms: D000595:Amino Acid Sequence; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011233:Precipitin Tests; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D019473:Transcription Factors, TFII / Q000737:chemistry / Q000502:physiology*; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D000099250:DNA Excision Repair Protein ERCC-5