Sequential recruitment of the repair factors during NER: the role of XPG in initiating the resynthesis step.
Fiche publication
Date publication
janvier 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr EGLY Jean-Marc
Tous les auteurs :
Mocquet V, Laine JP, Riedl T, Yajin Z, Lee MY, Egly JM
Lien Pubmed
Résumé
To address the biochemical mechanisms underlying the coordination between the various proteins required for nucleotide excision repair (NER), we employed the immobilized template system. Using either wild-type or mutated recombinant proteins, we identified the factors involved in the NER process and showed the sequential comings and goings of these factors to the immobilized damaged DNA. Firstly, we found that PCNA and RF-C arrival requires XPF 5' incision. Moreover, the positioning of RF-C is facilitated by RPA and induces XPF release. Concomitantly, XPG leads to PCNA recruitment and stabilization. Our data strongly suggest that this interaction with XPG protects PCNA and Pol delta from the effect of inhibitors such as p21. XPG and RPA are released as soon as Pol delta is recruited by the RF-C/PCNA complex. Finally, a ligation system composed of FEN1 and Ligase I can be recruited to fully restore the DNA. In addition, using XP or trichothiodystrophy patient-derived cell extracts, we were able to diagnose the biochemical defect that may prove to be important for therapeutic purposes.
Référence
EMBO J. 2008 Jan 9;27(1):155-67