ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs

Kerry W. Brookman, Jane E. Lamerdin, Michael P. Thelen, Mona Hwang, Joyce T. Reardon, Aziz Sancar, Zi Qiang Zhou, Christi A. Walter, Christopher N. Parris, Larry H. Thompson

Research output: Contribution to journalArticle

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Abstract

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, FRCC4 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.

Original languageEnglish (US)
Pages (from-to)6553-6562
Number of pages10
JournalMolecular and Cellular Biology
Volume16
Issue number11
StatePublished - 1996
Externally publishedYes

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DNA Repair
Genetic Recombination
Proteins
Genes
Complementary DNA
Chromosomes, Human, Pair 16
Xeroderma Pigmentosum
Cosmids
DNA Adducts
Schizosaccharomyces
Papio
Essential Genes
Meiosis
Cricetulus
Drosophila melanogaster
Saccharomyces cerevisiae
Testis
Ovary
Rodentia
Chromosomes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Brookman, K. W., Lamerdin, J. E., Thelen, M. P., Hwang, M., Reardon, J. T., Sancar, A., ... Thompson, L. H. (1996). ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs. Molecular and Cellular Biology, 16(11), 6553-6562.

ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs. / Brookman, Kerry W.; Lamerdin, Jane E.; Thelen, Michael P.; Hwang, Mona; Reardon, Joyce T.; Sancar, Aziz; Zhou, Zi Qiang; Walter, Christi A.; Parris, Christopher N.; Thompson, Larry H.

In: Molecular and Cellular Biology, Vol. 16, No. 11, 1996, p. 6553-6562.

Research output: Contribution to journalArticle

Brookman, KW, Lamerdin, JE, Thelen, MP, Hwang, M, Reardon, JT, Sancar, A, Zhou, ZQ, Walter, CA, Parris, CN & Thompson, LH 1996, 'ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs', Molecular and Cellular Biology, vol. 16, no. 11, pp. 6553-6562.
Brookman KW, Lamerdin JE, Thelen MP, Hwang M, Reardon JT, Sancar A et al. ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs. Molecular and Cellular Biology. 1996;16(11):6553-6562.
Brookman, Kerry W. ; Lamerdin, Jane E. ; Thelen, Michael P. ; Hwang, Mona ; Reardon, Joyce T. ; Sancar, Aziz ; Zhou, Zi Qiang ; Walter, Christi A. ; Parris, Christopher N. ; Thompson, Larry H. / ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs. In: Molecular and Cellular Biology. 1996 ; Vol. 16, No. 11. pp. 6553-6562.
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abstract = "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, FRCC4 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.",
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AU - Brookman, Kerry W.

AU - Lamerdin, Jane E.

AU - Thelen, Michael P.

AU - Hwang, Mona

AU - Reardon, Joyce T.

AU - Sancar, Aziz

AU - Zhou, Zi Qiang

AU - Walter, Christi A.

AU - Parris, Christopher N.

AU - Thompson, Larry H.

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