ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs.
ERCC4 is an essential human gene in the nucleotide excision repair (NER) pathway, which is responsible for removing UV-C photoproducts and bulky adducts from DNA. Among the NER genes, ERCC4 and ERCC1 are also uniquely 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 gene structure and functional cDNA sequence encoding a 916-amino-acid protein (104 kDa), which has substantial homology with the eukaryotic DNA repair and recombination proteins MEI-9 (Drosophila melanogaster), Rad16 (Schizosaccharomyces pombe), and Rad1 (Saccharomyces cerevisiae). ERCC4 cDNA efficiently corrected mutants in rodent NER complementation groups 4 and 11, showing the equivalence of these groups, and ERCC4 protein levels were reduced in mutants of both groups. In cells of an XP-F patient, the ERCC4 protein level was reduced to less than 5%, consistent with XPF being the ERCC4 gene. The considerable identity (40%) between ERCC4 and MEI-9 suggests a possible involvement of ERCC4 in meiosis. In baboon tissues, ERCC4 was expressed weakly and was not significantly higher in testis than in nonmeiotic tissues.
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94551-0808, USA.
K W
KW
Brookman
J E
JE
Lamerdin
M P
MP
Thelen
M
M
Hwang
J T
JT
Reardon
A
A
Sancar
Z Q
ZQ
Zhou
C A
CA
Walter
C N
CN
Parris
L H
LH
Thompson
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002470:Cell Survival / Q000528:radiation effects; D003001:Cloning, Molecular; D003360:Cosmids; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D004720:Endonucleases / Q000737:chemistry; D005091:Exons; D005656:Fungal Proteins / Q000737:chemistry; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D016366:Open Reading Frames; D010215:Papio; D011506:Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000096:biosynthesis; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; C097527:MEI-9 protein, Drosophila; D009687:Nuclear Proteins; D011506:Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C095888:xeroderma pigmentosum group F protein; D004720:Endonucleases; C069266:RAD1 protein, S cerevisiae; C499354:rad1 protein, S pombe; D045643:DNA Repair Enzymes