title: p8/TTD-A as a repair-specific TFIIH subunit.
abstract: How subunits of the transcription/repair factor TFIIH cooperate to allow for the removal of DNA lesions or for the transcription of genes is crucial to understand the functioning of this complex. Here, we reveal that p8/TTD-A, the tenth subunit of TFIIH, has a critical role in DNA repair where it triggers DNA opening by stimulating XPB ATPase activity together with the damage recognition factor XPC-hHR23B. Fluorescent antibody labeling shows that such opening is needed for the recruitment of XPA to the site of the damage. By contrast, p8 is dispensable for RNA synthesis and doesn't interfere with the transcriptional function of CAK, although both interact with the XPD subunit. Interestingly, p8 overexpression in TTD-XPD cells counteracts the detrimental effect of XPD mutations by restoring the cellular TFIIH concentration. These findings resolve the primary functions of p8 and unveil how TFIIH components specifically direct the complex toward repair or transcription.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université Louis Pasteur, BP 163, 67404 Illkirch Cedex, C. U. Strasbourg, France. fredr@igbmc.u-strasbg.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Coin
authors.forename: Luca
authors.initials: L
authors.lastname: Proietti De Santis
authors.forename: Tiziana
authors.initials: T
authors.lastname: Nardo
authors.forename: Olga
authors.initials: O
authors.lastname: Zlobinskaya
authors.forename: Miria
authors.initials: M
authors.lastname: Stefanini
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Egly
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D021122:Protein Subunits; D011994:Recombinant Proteins; D051758:Transcription Factor TFIIH; D004247:DNA; D000251:Adenosine Triphosphatases