Article
- The EMBO Journal (2008) 27, 155 - 167
- doi:10.1038/sj.emboj.7601948
Published online: 13 December 2007
Subject Category:
Sequential recruitment of the repair factors during NER: the role of XPG in initiating the resynthesis step
Vincent Mocquet1, Jean Philippe Lainé1, Thilo Riedl1, Zhou Yajin2, Marietta Y Lee2 and Jean Marc Egly1
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch Cedex, France
- Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA
Correspondence to:
Jean Marc Egly, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, BP 163, Illkirch Cedex 67404, France. Tel.: +33 388 65 34 47; Fax: +33 388 65 32 01; E-mail: egly@igbmc.u-strasbg.fr
Received 22 August 2007; Accepted 14 November 2007
Abstract
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
from the effect of inhibitors such as p21. XPG and RPA are released as soon as Pol 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.
Keywords:
- DNA resynthesis,
- nucleotide excision repair,
- XPG
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