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Gene Review

ERCC3  -  excision repair cross-complementation group 3

Homo sapiens

Synonyms: BTF2, BTF2 p89, Basic transcription factor 2 89 kDa subunit, DNA excision repair protein ERCC-3, DNA repair protein complementing XP-B cells, ...
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Disease relevance of ERCC3

  • The observation that the largest subunit of TFIIH is the excision-repair protein XPB/ERCC3 (ref. 1), a helicase implicated in the human DNA-repair disorders xeroderma pigmentosum (XP) and Cockayne's syndrome, suggests a functional link between transcription and DNA repair [1].
  • Two of them, ERCC2 and ERCC3, are responsible for atypical forms of XP disorders which confer a high predisposition to skin cancer [2].
  • These findings indicate that these tagSNPs of the ERCC2 and ERCC3 along with their surrounding regions may serve as biomarkers of susceptibility to lung cancer, which warrant further validation by other population-based and phenotypic studies to determine the biological relevance of these tagSNPs [3].
  • Comparative analyses of relative ERCC3 and ERCC6 mRNA levels in gliomas and adjacent non-neoplastic brain [4].
  • In the presence of a reverse transcription inhibitor, the HIV cDNA appeared more stable in mutant XPB or XPD cells [5].

Psychiatry related information on ERCC3

  • Careful analysis of each TFIIH subunit also shows how the p44 Ring finger participates in certain promoter escape reactions [6].

High impact information on ERCC3


Chemical compound and disease context of ERCC3

  • Two distinct clinical phenotypes, xeroderma pigmentosum associated with Cockayne's syndrome (XP/CS) and trichothiodystrophy (TTD), can be due to mutations in the XPB gene [11].

Biological context of ERCC3

  • Molecular analysis of the ERCC3 gene in both patients revealed a single base substitution causing a missense mutation in a region that is completely conserved in yeast, Drosophila, mouse, and human ERCC3 [12].
  • Transfection and microinjection experiments demonstrated that mutations in ERCC3 are responsible for XP complementation group B, a very rare form of XP that is simultaneously associated with Cockayne's syndrome (CS) [13].
  • Chromosome 2 corrected UV24, and the gene responsible was designated ERCC3 [14].
  • We find that TFIIH has a dual role, being required for basal transcription of class II genes and for participation in DNA-excision repair [1].
  • The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway [15].

Anatomical context of ERCC3


Associations of ERCC3 with chemical compounds

  • Using filter binding as well as in vitro transcription challenge competition assays, we now show that the promoter recognition factor TATA box-binding protein (TBP)/TFIID binds selectively to and is sequestered by cisplatin- or UV-damaged DNA, either alone or in the context of a larger protein complex including TFIIH [21].
  • This transcription was well correlated with TFIIE stimulated TFIIH phosphorylation of serine at position 5 (Ser-5) within the heptapeptide repeat of the PolII CTD [22].
  • Upon stimulation of the cells by TNF-alpha, NF-kappaB and TFIIH are rapidly recruited to the promoter together with additional Mediator and RNAP II, but CDK8 is lost [23].
  • In the present work, we studied cellular DNA repair properties of skin fibro-blasts from two patients mutated in the XPB gene: an XP/CS patient cell (XPCS2BA) with a T296C (F99S) transition and a TTD patient cell (TTD6VI) exhibiting an A355C (T119P) transversion [11].
  • Structural characterization of the cysteine-rich domain of TFIIH p44 subunit [24].

Physical interactions of ERCC3

  • Although the biological significance of the binding remains to be uncovered, BCR binds to the XPB/p62 complex [25].
  • In contrast, the human damage recognition protein XPA specifically binds to TFIIH and apparently recruits it to the damage site [26].

Enzymatic interactions of ERCC3

  • The binding appeared to be required for XPB to be tyrosine-phosphorylated by BCR-ABL [27].

Other interactions of ERCC3

  • This deficiency can be rescued by transferring the wild-type XPB or XPD gene into the corresponding mutant cells [15].
  • Here we have extended these studies to compare low-grade tumors to high-grade tumors and to include ERCC3 (which links DNA repair with DNA transcription) and ERCC6 (which is essential for gene-specific repair) [4].
  • In contrast, both ERCC1 and ERCC3 were 10- and 1.5-fold lower in ADDP cells compared to A2780 [28].
  • The total cellular levels of XPC and XPB were similar in both p53-WT and -Null cells and remained unchanged up to 24h following UV irradiation [29].
  • Replicating Moloney murine leukemia virus viral production was greater in XPB or XPD mutant cells but not XPA mutant cells [5].

Analytical, diagnostic and therapeutic context of ERCC3

  • Microinjection experiments suggest that exogenous ERCC3 can exchange with ERCC3 subunits in the complex [30].
  • In this case-control study of 1,010 incident lung cancer cases and 1,011 age and sex frequency-matched cancer-free controls in a Chinese population, we genotyped eight tagging polymorphisms of ERCC2 and ERCC3 using the high-throughput Taqman platform to determine their associations with risk of lung cancer [3].
  • Quantitative PCR showed an increase in total cDNA molecules, integrated provirus, and 2LTR circles in XPB and XPD mutant cells [5].
  • To examine the significance of the postulated functional domains in ERCC3, we have introduced mutations in the ERCC3 cDNA by means of site-specific mutagenesis and have determined the repair capacity of each mutant to complement the UV-sensitive phenotype of rodent group 3 cells [31].
  • Single particles of human TFIIH were revealed by electron microscopy and image processing at a resolution of 3.8 nm [32].


  1. Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II. Drapkin, R., Reardon, J.T., Ansari, A., Huang, J.C., Zawel, L., Ahn, K., Sancar, A., Reinberg, D. Nature (1994) [Pubmed]
  2. The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor. Schaeffer, L., Moncollin, V., Roy, R., Staub, A., Mezzina, M., Sarasin, A., Weeda, G., Hoeijmakers, J.H., Egly, J.M. EMBO J. (1994) [Pubmed]
  3. Polymorphisms in the two helicases ERCC2/XPD and ERCC3/XPB of the transcription factor IIH complex and risk of lung cancer: a case-control analysis in a Chinese population. Hu, Z., Xu, L., Shao, M., Yuan, J., Wang, Y., Wang, F., Yuan, W., Qian, J., Ma, H., Wang, Y., Liu, H., Chen, W., Yang, L., Jing, G., Huo, X., Chen, F., Jin, L., Wei, Q., Wu, T., Lu, D., Huang, W., Shen, H. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  4. Comparative analyses of relative ERCC3 and ERCC6 mRNA levels in gliomas and adjacent non-neoplastic brain. Dabholkar, M.D., Berger, M.S., Vionnet, J.A., Overton, L., Thompson, C., Bostick-Bruton, F., Yu, J.J., Silber, J.R., Reed, E. Mol. Carcinog. (1996) [Pubmed]
  5. The DNA repair genes XPB and XPD defend cells from retroviral infection. Yoder, K., Sarasin, A., Kraemer, K., McIlhatton, M., Bushman, F., Fishel, R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. The 14th Datta Lecture. TFIIH: from transcription to clinic. Egly, J.M. FEBS Lett. (2001) [Pubmed]
  7. Relationships between DNA repair and transcription. Friedberg, E.C. Annu. Rev. Biochem. (1996) [Pubmed]
  8. Common themes in assembly and function of eukaryotic transcription complexes. Zawel, L., Reinberg, D. Annu. Rev. Biochem. (1995) [Pubmed]
  9. 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]
  10. XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RARalpha. Keriel, A., Stary, A., Sarasin, A., Rochette-Egly, C., Egly, J.M. Cell (2002) [Pubmed]
  11. The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne's syndrome or trichothiodystrophy cellular phenotypes. Riou, L., Zeng, L., Chevallier-Lagente, O., Stary, A., Nikaido, O., Taïeb, A., Weeda, G., Mezzina, M., Sarasin, A. Hum. Mol. Genet. (1999) [Pubmed]
  12. Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3. Vermeulen, W., Scott, R.J., Rodgers, S., Müller, H.J., Cole, J., Arlett, C.F., Kleijer, W.J., Bootsma, D., Hoeijmakers, J.H., Weeda, G. Am. J. Hum. Genet. (1994) [Pubmed]
  13. Nucleotide excision repair syndromes: molecular basis and clinical symptoms. Bootsma, D., Weeda, G., Vermeulen, W., van Vuuren, H., Troelstra, C., van der Spek, P., Hoeijmakers, J. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1995) [Pubmed]
  14. Identification of nucleotide-excision-repair genes on human chromosomes 2 and 13 by functional complementation in hamster-human hybrids. Thompson, L.H., Carrano, A.V., Sato, K., Salazar, E.P., White, B.F., Stewart, S.A., Minkler, J.L., Siciliano, M.J. Somat. Cell Mol. Genet. (1987) [Pubmed]
  15. The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. Wang, X.W., Vermeulen, W., Coursen, J.D., Gibson, M., Lupold, S.E., Forrester, K., Xu, G., Elmore, L., Yeh, H., Hoeijmakers, J.H., Harris, C.C. Genes Dev. (1996) [Pubmed]
  16. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Erba, E., Bergamaschi, D., Bassano, L., Damia, G., Ronzoni, S., Faircloth, G.T., D'Incalci, M. Eur. J. Cancer (2001) [Pubmed]
  17. Characterization of ERCC3 mutations in the Chinese hamster ovary 27-1, UV24 and MMC-2 cell lines. Hall, H., Gurský, J., Nicodemou, A., Rybanská, I., Kimlícková, E., Pirsel, M. Mutat. Res. (2006) [Pubmed]
  18. Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue. Jaitovich-Groisman, I., Benlimame, N., Slagle, B.L., Perez, M.H., Alpert, L., Song, D.J., Fotouhi-Ardakani, N., Galipeau, J., Alaoui-Jamali, M.A. J. Biol. Chem. (2001) [Pubmed]
  19. Localization of the xeroderma pigmentosum group B-correcting gene ERCC3 to human chromosome 2q21. Weeda, G., Wiegant, J., van der Ploeg, M., Geurts van Kessel, A.H., van der Eb, A.J., Hoeijmakers, J.H. Genomics (1991) [Pubmed]
  20. Excision repair cross complementing 3 expression is involved in patient prognosis and tumor progression in esophageal cancer. Terashita, Y., Ishiguro, H., Haruki, N., Sugiura, H., Tanaka, T., Kimura, M., Shinoda, N., Kuwabara, Y., Fujii, Y. Oncol. Rep. (2004) [Pubmed]
  21. Cisplatin- and UV-damaged DNA lure the basal transcription factor TFIID/TBP. Vichi, P., Coin, F., Renaud, J.P., Vermeulen, W., Hoeijmakers, J.H., Moras, D., Egly, J.M. EMBO J. (1997) [Pubmed]
  22. Modulation of TFIIH-associated kinase activity by complex formation and its relationship with CTD phosphorylation of RNA polymerase II. Watanabe, Y., Fujimoto, H., Watanabe, T., Maekawa, T., Masutani, C., Hanaoka, F., Ohkuma, Y. Genes Cells (2000) [Pubmed]
  23. Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency. Kim, Y.K., Bourgeois, C.F., Pearson, R., Tyagi, M., West, M.J., Wong, J., Wu, S.Y., Chiang, C.M., Karn, J. EMBO J. (2006) [Pubmed]
  24. Structural characterization of the cysteine-rich domain of TFIIH p44 subunit. Fribourg, S., Kellenberger, E., Rogniaux, H., Poterszman, A., Van Dorsselaer, A., Thierry, J.C., Egly, J.M., Moras, D., Kieffer, B. J. Biol. Chem. (2000) [Pubmed]
  25. BCR binds to the xeroderma pigmentosum group B protein. Maru, Y., Kobayashi, T., Tanaka, K., Shibuya, M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  26. The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor. Park, C.H., Mu, D., Reardon, J.T., Sancar, A. J. Biol. Chem. (1995) [Pubmed]
  27. The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein. Takeda, N., Shibuya, M., Maru, Y. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  28. Effects of gemcitabine on cis-platinum-DNA adduct formation and repair in a panel of gemcitabine and cisplatin-sensitive or -resistant human ovarian cancer cell lines. Peters, G.J., Van Moorsel, C.J., Lakerveld, B., Smid, K., Noordhuis, P., Comijn, E.C., Weaver, D., Willey, J.C., Voorn, D., Van der Vijgh, W.J., Pinedo, H.M. Int. J. Oncol. (2006) [Pubmed]
  29. 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]
  30. Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH). van Vuuren, A.J., Vermeulen, W., Ma, L., Weeda, G., Appeldoorn, E., Jaspers, N.G., van der Eb, A.J., Bootsma, D., Hoeijmakers, J.H., Humbert, S. EMBO J. (1994) [Pubmed]
  31. Mutational analysis of ERCC3, which is involved in DNA repair and transcription initiation: identification of domains essential for the DNA repair function. Ma, L., Westbroek, A., Jochemsen, A.G., Weeda, G., Bosch, A., Bootsma, D., Hoeijmakers, J.H., van der Eb, A.J. Mol. Cell. Biol. (1994) [Pubmed]
  32. Molecular structure of human TFIIH. Schultz, P., Fribourg, S., Poterszman, A., Mallouh, V., Moras, D., Egly, J.M. Cell (2000) [Pubmed]
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