Nucleotide excision repair (NER), one of the major cellular DNA repair systems, removes a wide range of lesions in a multi-enzyme reaction. In man, a NER defect due to a mutation in one of at least 11 distinct genes, can give rise to the inherited repair disorders xeroderma pigmentosum (XP), Cockayne's syndrome or PIBIDS, a photosensitive form of the brittle hair disease trichothiodystrophy. Laboratory-induced NER-deficient mutants of cultured rodent cells have been classified into 11 complementation groups (CGs). Some of these have been shown to correspond with human disorders. In cell-free extracts prepared from rodent CGs 1-5 and 11, but not in a mutant from CG6, we find an impaired repair of damage induced in plasmids by UV light and N-acetoxy-acetylaminofluorene. Complementation analysis in vitro of rodent CGs is accomplished by pairwise mixing of mutant extracts. The results show that mutants from groups 2, 3, 5 and XP-A can complement all other CGs tested. However, selective non-complementation in vitro was observed in mutual mixtures of groups 1, 4, 11 and XP-F, suggesting that the complementing activities involved somehow affect each other. Depletion of wild-type human extracts from ERCC1 protein using specific anti-ERCC1 antibodies concomitantly removed the correcting activities for groups 4, 11 and XP-F, but not those for the other CGs. Furthermore, we find that 33 kDa ERCC1 protein sediments as a high mol. wt species of approximately 120 kDa in a native glycerol gradient.

*DNA Damage, *DNA Repair, *Endonucleases, 0 (Antibodies), 0 (DNA-Binding Proteins), 0 (ERCC4 protein), 0 (Fungal Proteins), 0 (Plasmids), 0 (Proteins), 0 (RAD1 protein, S cerevisiae), 6098-44-8 (Acetoxyacetylaminofluorene), Acetoxyacetylaminofluorene/toxicity, Animals, Antibodies/pharmacology, CHO Cells, Cell-Free System, Cockayne Syndrome/genetics, Comparative Study, DNA-Binding Proteins/metabolism, EC 3.1.- (ERCC-1 protein, human), EC 3.1.- (Endonucleases), EC 3.1.- (RAD10 protein, S cerevisiae), Fungal Proteins/metabolism, Genetic Complementation Test, Hamsters, Human, Mutation, Plasmids/drug effects/radiation effects, Proteins/genetics/immunology/*metabolism, Saccharomyces cerevisiae/metabolism, Support, Non-U.S. Gov't, Transfection, Translation, Genetic, Ultraviolet Rays, Xeroderma Pigmentosum/*genetics/metabolism
EMBO Journal
Erasmus MC: University Medical Center Rotterdam

van Vuuren, A.J, Appeldoorn, E, Odijk, H, Yasui, A, Jaspers, N.G.J, Bootsma, D, & Hoeijmakers, J.H.J. (1993). Evidence for a repair enzyme complex involving ERCC1, and the correcting activities of ERCC4, ERCC11 and the xeroderma pigmentosum group F. EMBO Journal, 12, 3693–3701. Retrieved from