p8/TTD-A as a repair-specific TFIIH subunit.
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.
Coin
Frédéric
F
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
Proietti De Santis
Luca
L
Nardo
Tiziana
T
Zlobinskaya
Olga
O
Stefanini
Miria
M
Egly
Jean-Marc
JM
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
D021122:Protein Subunits; D011994:Recombinant Proteins; D051758:Transcription Factor TFIIH; D004247:DNA; D000251:Adenosine Triphosphatases