p8/TTD-A as a repair-specific TFIIH subunit.
Fiche publication
Date publication
janvier 2006
Auteurs
Membres identifiés du Cancéropôle Est :
Dr COIN Frédéric, Dr EGLY Jean-Marc
Tous les auteurs :
Coin F, Proietti De Santis L, Nardo T, Zlobinskaya O, Stefanini M, Egly JM
Lien Pubmed
Résumé
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.
Référence
Mol Cell. 2006 Jan 20;21(2):215-26.