Nucleotide excision repair driven by the dissociation of CAK from TFIIH.
Fiche publication
Date publication
juillet 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr COIN Frédéric, Dr EGLY Jean-Marc
Tous les auteurs :
Coin F, Oksenych V, Mocquet V, Groh S, Blattner C, Egly JM
Lien Pubmed
Résumé
The transcription/DNA repair factor TFIIH is organized into a core that associates with the CDK-activating kinase (CAK) complex. Using chromatin immunoprecipitation, we have followed the composition of TFIIH over time after UV irradiation of repair-proficient or -deficient human cells. We show that TFIIH changes subunit composition in response to DNA damage. The CAK is released from the core during nucleotide excision repair (NER). Using reconstituted in vitro NER assay, we show that XPA catalyzes the detachment of the CAK from the core, together with the arrival of the other NER-specific factors. The release of the CAK from the core TFIIH promotes the incision/excision of the damaged oligonucleotide and thereby the repair of the DNA. Following repair, the CAK reappears with the core TFIIH on the chromatin, together with the resumption of transcription. Our findings demonstrate that the composition of TFIIH is dynamic to adapt its engagement in distinct cellular processes.
Référence
Mol Cell. 2008 Jul 11;31(1):9-20.