The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ERCC5  -  excision repair cross-complementation group 5

Homo sapiens

Synonyms: COFS3, DNA excision repair protein ERCC-5, DNA repair protein complementing XP-G cells, ERCC5-201, ERCM2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ERCC5

  • The human XPG (ERCC5) gene encodes a large acidic protein that corrects the ultraviolet light sensitivity of cells from both xeroderma pigmentosum complementation group G and rodent ERCC group 5 [1].
  • Loss of a nonenzymatic function of XPG results in defective transcription-coupled repair (TCR), Cockayne syndrome (CS), and early death, but the molecular basis for these phenotypes is unknown [2].
  • In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13-1.88; P = 0.004), DLBCL (OR: 1.44; 95% CI: 0.99-2.09; P = 0.058), and also T cell lymphoma [3].
  • An XPG DNA repair defect causing mutagen hypersensitivity in mouse leukemia L1210 cells [4].
  • Here we report the isolation of full-length XPG as a soluble protein expressed from a recombinant baculovirus [5].

High impact information on ERCC5

  • Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome [6].
  • In addition to xeroderma pigmentosum, mutations in the human XPG gene cause early onset Cockayne syndrome (CS) [7].
  • This structure suggests the way in which the widely separated conserved regions in the larger nucleotide excision repair proteins, such as human XPG, could assemble into a structure like that of the smaller replication nucleases [8].
  • Expression of the human cDNA in vivo restores to normal the sensitivity to ultraviolet light and unscheduled DNA synthesis of lymphoblastoid cells from XP group G, but not CS group A. The XP-G correcting protein XPGC is generated from a messenger RNA of approximately 4 kilobases that is present in normal amounts in the XP-G cell line [9].
  • Polarity appears crucial for positioning of the excision repair nucleases XPG and ERCC1-XPF on the DNA [10].

Chemical compound and disease context of ERCC5


Biological context of ERCC5

  • Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe [16].
  • The complete deduced amino acid sequence of ERCC5 was reconstructed from several cDNA clones encoding a predicted protein of 1,186 amino acids [16].
  • The cloned human sequences exhibited 100% concordance with the locus designated genetically as ERCC5 located on human chromosome 13q [17].
  • Analysis of transformants derived from the active cosmid pairs showed that the functional 32-kbp ERCC5 gene was reconstructed by homologous intercosmid recombination [17].
  • Transfection with mouse ERCC5 cDNA restored normal levels of UV resistance to XL216 cells [18].

Anatomical context of ERCC5


Associations of ERCC5 with chemical compounds

  • A conserved arginine in FEN-1 (Arg339) and XPG (Arg992) was found to be crucial for PCNA binding activity [22].
  • In contrast, expression of the XPG endonuclease was correlated with the cytotoxicity for irofulven and, to a lesser degree, for cisplatin [19].
  • We have observed that mutation of the XPG gene drastically reduced the level and rate of global removal of thymine glycol (induced by 2-Gy irradiation), and there was no evidence for an inducible response [23].
  • This changed the highly conserved Pro-72 to a histidine, a substitution that would be expected to seriously impair the 3' endonuclease function of XPG in nucleotide excision repair [24].
  • In addition, exposure of XPA and XPG fibroblasts to UV (5, 10 or 20 J/m2) followed by incubation without araC resulted in a strong upregulation of p53 [25].

Physical interactions of ERCC5

  • We show that XPG interacts with elongating RNA polymerase II (RNAPII) in the cell and binds stalled RNAPII ternary complexes in vitro both independently and cooperatively with CSB [2].
  • XPG binding stabilizes the NER preincision complex and is essential for the 5' incision by the ERCC1/XPF endonuclease [26].
  • Using extracts from A23187-treated cells, a similar conclusion was drawn except that the inhibitory effect of cytosolic extracts on UVDRP binding was completely diminished by proteinase K [27].

Regulatory relationships of ERCC5


Other interactions of ERCC5

  • During nucleotide excision repair in human cells, a damaged DNA strand is cleaved by two endonucleases, XPG on the 3' side of the lesion and ERCC1-XPF on the 5' side [28].
  • The results obtained from our immunoprecipitation experiment further demonstrated that the ATM protein interacted with the TFIIH basal transcription factor and the XPG protein of the NER pathway [11].
  • The human cell lines, defective in nucleotide excision protein, such as xeroderma pigmentosum (XP) A, XPD, and XPG, excised Ultraviolet C-induced adducts less rapidly than normal fibroblasts, but excised As(2)O(3) adducts at the same rate as the normal cells [29].
  • A moderate increase in the levels of SSBs was also found in individuals with the homozygous XPG exon 15 wild type (GG) and heterozygous (GC) genotypes in comparison to those with the homozygous (CC) genotype (P=0.066) and in individuals with low activity EPHX1 genotype in comparison to those with high activity genotype [30].
  • Such dispersal requires functional XPA, XPF and XPG proteins [31].

Analytical, diagnostic and therapeutic context of ERCC5


  1. Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient. Nouspikel, T., Clarkson, S.G. Hum. Mol. Genet. (1994) [Pubmed]
  2. Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome. Sarker, A.H., Tsutakawa, S.E., Kostek, S., Ng, C., Shin, D.S., Peris, M., Campeau, E., Tainer, J.A., Nogales, E., Cooper, P.K. Mol. Cell (2005) [Pubmed]
  3. Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut. Shen, M., Zheng, T., Lan, Q., Zhang, Y., Zahm, S.H., Wang, S.S., Holford, T.R., Leaderer, B., Yeager, M., Welch, R., Kang, D., Boyle, P., Zhang, B., Zou, K., Zhu, Y., Chanock, S., Rothman, N. Hum. Genet. (2006) [Pubmed]
  4. An XPG DNA repair defect causing mutagen hypersensitivity in mouse leukemia L1210 cells. Vilpo, J.A., Vilpo, L.M., Szymkowski, D.E., O'Donovan, A., Wood, R.D. Mol. Cell. Biol. (1995) [Pubmed]
  5. Isolation of active recombinant XPG protein, a human DNA repair endonuclease. O'Donovan, A., Scherly, D., Clarkson, S.G., Wood, R.D. J. Biol. Chem. (1994) [Pubmed]
  6. Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome. Le Page, F., Kwoh, E.E., Avrutskaya, A., Gentil, A., Leadon, S.A., Sarasin, A., Cooper, P.K. Cell (2005) [Pubmed]
  7. Requirement of yeast RAD2, a homolog of human XPG gene, for efficient RNA polymerase II transcription. implications for Cockayne syndrome. Lee, S.K., Yu, S.L., Prakash, L., Prakash, S. Cell (2002) [Pubmed]
  8. Structure of bacteriophage T4 RNase H, a 5' to 3' RNA-DNA and DNA-DNA exonuclease with sequence similarity to the RAD2 family of eukaryotic proteins. Mueser, T.C., Nossal, N.G., Hyde, C.C. Cell (1996) [Pubmed]
  9. Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2. Scherly, D., Nouspikel, T., Corlet, J., Ucla, C., Bairoch, A., Clarkson, S.G. Nature (1993) [Pubmed]
  10. DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair. de Laat, W.L., Appeldoorn, E., Sugasawa, K., Weterings, E., Jaspers, N.G., Hoeijmakers, J.H. Genes Dev. (1998) [Pubmed]
  11. The Involvement of Ataxia-telangiectasia Mutated Protein Activation in Nucleotide Excision Repair-facilitated Cell Survival with Cisplatin Treatment. Colton, S.L., Xu, X.S., Wang, Y.A., Wang, G. J. Biol. Chem. (2006) [Pubmed]
  12. Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome. Le Page, F., Kwoh, E.E., Avrutskaya, A., Gentil, A., Leadon, S.A., Sarasin, A., Cooper, P.K. Cell (2000) [Pubmed]
  13. Nucleotide excision repair 3' endonuclease XPG stimulates the activity of base excision repairenzyme thymine glycol DNA glycosylase. Bessho, T. Nucleic Acids Res. (1999) [Pubmed]
  14. XPG protein has a structure-specific endonuclease activity. Cloud, K.G., Shen, B., Strniste, G.F., Park, M.S. Mutat. Res. (1995) [Pubmed]
  15. Altered gene expression in human cells treated with the insecticide diazinon: correlation with decreased DNA excision repair capacity. Mankame, T., Hokanson, R., Fudge, R., Chowdhary, R., Busbee, D. Human & experimental toxicology. (2006) [Pubmed]
  16. Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe. MacInnes, M.A., Dickson, J.A., Hernandez, R.R., Learmonth, D., Lin, G.Y., Mudgett, J.S., Park, M.S., Schauer, S., Reynolds, R.J., Strniste, G.F. Mol. Cell. Biol. (1993) [Pubmed]
  17. Isolation of the functional human excision repair gene ERCC5 by intercosmid recombination. Mudgett, J.S., MacInnes, M.A. Genomics (1990) [Pubmed]
  18. An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum. Shiomi, T., Harada, Y., Saito, T., Shiomi, N., Okuno, Y., Yamaizumi, M. Mutat. Res. (1994) [Pubmed]
  19. Irofulven cytotoxicity depends on transcription-coupled nucleotide excision repair and is correlated with XPG expression in solid tumor cells. Koeppel, F., Poindessous, V., Lazar, V., Raymond, E., Sarasin, A., Larsen, A.K. Clin. Cancer Res. (2004) [Pubmed]
  20. The cdk7-cyclin H-MAT1 complex associated with TFIIH is localized in coiled bodies. Jordan, P., Cunha, C., Carmo-Fonseca, M. Mol. Biol. Cell (1997) [Pubmed]
  21. Ultraviolet-induced movement of the human DNA repair protein, Xeroderma pigmentosum type G, in the nucleus. Park, M.S., Knauf, J.A., Pendergrass, S.H., Coulon, C.H., Strniste, G.F., Marrone, B.L., MacInnes, M.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  22. The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21. Gary, R., Ludwig, D.L., Cornelius, H.L., MacInnes, M.A., Park, M.S. J. Biol. Chem. (1997) [Pubmed]
  23. Factors influencing the removal of thymine glycol from DNA in gamma-irradiated human cells. Weinfeld, M., Xing, J.Z., Lee, J., Leadon, S.A., Cooper, P.K., Le, X.C. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  24. Xeroderma pigmentosum group G with severe neurological involvement and features of Cockayne syndrome in infancy. Zafeiriou, D.I., Thorel, F., Andreou, A., Kleijer, W.J., Raams, A., Garritsen, V.H., Gombakis, N., Jaspers, N.G., Clarkson, S.G. Pediatr. Res. (2001) [Pubmed]
  25. Lack of correlation between DNA strand breakage and p53 protein levels in human fibroblast strains exposed to ultraviolet lights. Enns, L., Murray, D., Mirzayans, R. Photochem. Photobiol. (2000) [Pubmed]
  26. Recruitment of the Nucleotide Excision Repair Endonuclease XPG to Sites of UV-Induced DNA Damage Depends on Functional TFIIH. Zotter, A., Luijsterburg, M.S., Warmerdam, D.O., Ibrahim, S., Nigg, A., van Cappellen, W.A., Hoeijmakers, J.H., van Driel, R., Vermeulen, W., Houtsmuller, A.B. Mol. Cell. Biol. (2006) [Pubmed]
  27. Inhibition of UV-damaged DNA recognition activity in HeLa cells by calcium ionophore A23187: potential involvement of cytosolic proteins. Chao, C.C., Huang, S.L. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  28. Mechanism of open complex and dual incision formation by human nucleotide excision repair factors. Evans, E., Moggs, J.G., Hwang, J.R., Egly, J.M., Wood, R.D. EMBO J. (1997) [Pubmed]
  29. 8-Oxoguanine DNA Glycosylase and MutY Homolog Are Involved in the Incision of Arsenite-Induced DNA Adducts. Pu, Y.S., Jan, K.Y., Wang, T.C., Wang, A.S., Gurr, J.R. Toxicol. Sci. (2007) [Pubmed]
  30. Genetic polymorphisms and possible gene-gene interactions in metabolic and DNA repair genes: effects on DNA damage. Naccarati, A., Soucek, P., Stetina, R., Haufroid, V., Kumar, R., Vodickova, L., Trtkova, K., Dusinska, M., Hemminki, K., Vodicka, P. Mutat. Res. (2006) [Pubmed]
  31. Tumor suppressor p53 dependent recruitment of nucleotide excision repair factors XPC and TFIIH to DNA damage. Wang, Q.E., Zhu, Q., Wani, M.A., Wani, G., Chen, J., Wani, A.A. DNA Repair (Amst.) (2003) [Pubmed]
  32. Precise localization of the excision repair gene, ERCC5, to human chromosome 13q32.3-q33.1 by direct R-banding fluorescence in situ hybridization. Takahashi, E., Shiomi, N., Shiomi, T. Jpn. J. Cancer Res. (1992) [Pubmed]
  33. The spacer region of XPG mediates recruitment to nucleotide excision repair complexes and determines substrate specificity. Dunand-Sauthier, I., Hohl, M., Thorel, F., Jaquier-Gubler, P., Clarkson, S.G., Schärer, O.D. J. Biol. Chem. (2005) [Pubmed]
  34. Enhancement of XPG mRNA transcription by human interferon-beta in Cockayne syndrome cells with complementation group B. Suzuki, Y., Sugita, K., Suzuki, N., Kita, K., Higuchi, Y., Yamaura, A., Kohno, Y. Int. J. Mol. Med. (1999) [Pubmed]
WikiGenes - Universities