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.
Brookman
K W
KW
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94551-0808, USA.
Lamerdin
J E
JE
Thelen
M P
MP
Hwang
M
M
Reardon
J T
JT
Sancar
A
A
Zhou
Z Q
ZQ
Walter
C A
CA
Parris
C N
CN
Thompson
L H
LH
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