Evidence for a repair enzyme complex involving ERCC1 and complementing activities of ERCC4, ERCC11 and xeroderma pigmentosum group F

A. J. Van Vuuren, E. Appeldoorn, H. Odijk, A. Yasui, N. G.J. Jaspers, D. Bootsma, J. H.J. Hoeijmakers

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153 Citaten (Scopus)


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 classifed 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 ~120 kDa in a native glycerol gradient. These results strongly suggest the presence of a pre-existing enzyme complex in mammalian cell extracts, harbouring at least the products of the ERCC1 and ERCC4 genes. This complex also carries complementing activities of XP group F and rodent CG11. We postulate that the complex, like the one in Saccharomyces cerevisiae involving the RAD1 and RAD10 proteins (the latter being the homologue of ERCC1), functions in both NER and recombinational repair.

Originele taal-2Engels
Pagina's (van-tot)3693-3701
Aantal pagina's9
TijdschriftEMBO Journal
Nummer van het tijdschrift9
StatusGepubliceerd - 1993
Extern gepubliceerdJa


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