ERCC4 (XPF) ENCODES A HUMAN NUCLEOTIDE EXCISION-REPAIR PROTEIN WITH EUKARYOTIC RECOMBINATION HOMOLOGS

ERCC4 is an essential human gene in the nucleotide excision repair (NE R) pathway, which is responsible for removing UV-C photoproducts and b ulky adducts from DNA, Among the NER genes, ERCC4 and EXCC1 are also u niquely involved in removing DNA interstrand cross-linking damage, The ERCC1-ERCC4 heterodimer, like the homologous Rad10-Rad1 complex, was recently found to possess an endonucleolytic activity that incises on the 5' side of damage, The ERCC4 gene, assigned to chromosome 16p13.1- p13.2, was previously isolated by using a chromosome 16 cosmid library . It corrects the defect in Chinese hamster ovary (CHO) mutants of NER complementation group 4 and is implicated in complementation group F of the human disorder xeroderma pigmentosum. We describe the ERCC4 gen e structure and functional cDNA sequence encoding a 916-amino-acid pro tein (104 kDa), which has substantial homology with the eukaryotic DNA repair and recombination proteins MEI-9 (Drosophila melanogaster), Ra d16 (Schizosaccharomyces pombe), and Radl (Saccharomyces cerevisiae). ERCC4 cDNA efficiently corrected mutants in rodent NER complementation groups 4 and 11, showing the equivalence of these groups, and ERCC4 p rotein levels were reduced in mutants of both groups, In cells of an X P-F patient, the ERCC4 protein level was reduced to less than 5%, cons istent with XPF being the ERCC4 gene, The considerable identity (40%) between ERCC4 and MEI-9 suggests a possible involvement of ERCC4 in me iosis. In baboon tissues, ERCC4 was expressed weakly and was not signi ficantly higher in testis than in nonmeiotic tissues.