Gene Symbol: Ercc6
Description: ERCC excision repair 6, chromatin remodeling factor
Alias: DNA excision repair protein ERCC-6, excision repair cross-complementation group 6, excision repair cross-complementing rodent repair deficiency, complementation group 6
Species: rat
Products:     Ercc6

Top Publications

  1. Gorgels T, van der Pluijm I, Brandt R, Garinis G, van Steeg H, van den Aardweg G, et al. Retinal degeneration and ionizing radiation hypersensitivity in a mouse model for Cockayne syndrome. Mol Cell Biol. 2007;27:1433-41 pubmed
  2. Christiansen M, Stevnsner T, Modin C, Martensen P, Brosh R, Bohr V. Functional consequences of mutations in the conserved SF2 motifs and post-translational phosphorylation of the CSB protein. Nucleic Acids Res. 2003;31:963-73 pubmed
    ..These observations may have significant implications for the function of CSB in vivo. ..
  3. Dianov G, Bischoff C, Sunesen M, Bohr V. Repair of 8-oxoguanine in DNA is deficient in Cockayne syndrome group B cells. Nucleic Acids Res. 1999;27:1365-8 pubmed
    ..We suggest that the CSB mutation leads to deficient transcription of the hOGG1 gene and thus to deficient repair of 8-oxoguanine in DNA...
  4. Xin B, Wang H. Identification of Two Novel ERCC6 Mutations in Old Order Amish with Cockayne Syndrome. Mol Syndromol. 2013;3:288-90 pubmed publisher
    ..Mutations in the DNA repair gene ERCC6 are responsible for the majority of CS cases reported...
  5. Henning K, Li L, Iyer N, McDaniel L, Reagan M, Legerski R, et al. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH. Cell. 1995;82:555-64 pubmed
    ..CSA protein interacts with CSB protein and with p44 protein, a subunit of the human RNA polymerase II transcription factor IIH. These observations suggest that the products of the CSA and CSB genes are involved in transcription. ..
  6. Lu Y, Lian H, Sharma P, Schreiber Agus N, Russell R, Chin L, et al. Disruption of the Cockayne syndrome B gene impairs spontaneous tumorigenesis in cancer-predisposed Ink4a/ARF knockout mice. Mol Cell Biol. 2001;21:1810-8 pubmed
  7. van der Horst G, van Steeg H, Berg R, van Gool A, de Wit J, Weeda G, et al. Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition. Cell. 1997;89:425-35 pubmed
    ..the nucleotide excision repair disorder Cockayne syndrome (CS) was generated by mimicking a truncation in the CSB(ERCC6) gene of a CS-B patient...
  8. Brosh R, Balajee A, Selzer R, Sunesen M, Proietti De Santis L, Bohr V. The ATPase domain but not the acidic region of Cockayne syndrome group B gene product is essential for DNA repair. Mol Biol Cell. 1999;10:3583-94 pubmed
    ..Thus the acidic region of CSB is likely to be dispensable for DNA repair, whereas the ATPase domain is essential for CSB function in both TCR-dependent and -independent pathways. ..
  9. Thorslund T, Von Kobbe C, Harrigan J, Indig F, Christiansen M, Stevnsner T, et al. Cooperation of the Cockayne syndrome group B protein and poly(ADP-ribose) polymerase 1 in the response to oxidative stress. Mol Cell Biol. 2005;25:7625-36 pubmed
    ..Our results implicate CSB in the PARP-1 poly(ADP-ribosyl)ation response after oxidative stress and thus suggest a novel role of CSB in the cellular response to oxidative damage. ..

More Information


  1. de Waard H, de Wit J, Gorgels T, van den Aardweg G, Andressoo J, Vermeij M, et al. Cell type-specific hypersensitivity to oxidative damage in CSB and XPA mice. DNA Repair (Amst). 2003;2:13-25 pubmed
    ..These findings establish the role of transcription-coupled repair in resistance to oxidative damage and reveal a cell- and organ-specific impact of this repair pathway to the clinical phenotype of CS and XP. ..
  2. Osterod M, Larsen E, Le Page F, Hengstler J, van der Horst G, Boiteux S, et al. A global DNA repair mechanism involving the Cockayne syndrome B (CSB) gene product can prevent the in vivo accumulation of endogenous oxidative DNA base damage. Oncogene. 2002;21:8232-9 pubmed
    ..The data indicate a role for Csb in the removal of 8-oxoG from the overall genome that is independent of both Ogg1-mediated base excision repair and regular transcription. ..
  3. Zhao X, Usdin K. Gender and cell-type-specific effects of the transcription-coupled repair protein, ERCC6/CSB, on repeat expansion in a mouse model of the fragile X-related disorders. Hum Mutat. 2014;35:341-9 pubmed
    ..Our data also show an unanticipated gender difference in instability even in Csb+/+ animals that may have implications for our understanding of the mechanism of repeat expansion in the FX mouse model and perhaps for humans as well. ..
  4. Yu S, Chen L, Ye L, Fei L, Tang W, Tian Y, et al. Identification of two missense mutations of ERCC6 in three Chinese sisters with Cockayne syndrome by whole exome sequencing. PLoS ONE. 2014;9:e113914 pubmed publisher
    ..Mutations of the ERCC6 and ERCC8 genes are the predominant cause of Cockayne syndrome, and the ERCC6 gene mutation is present in ..
  5. Trapp C, Reite K, Klungland A, Epe B. Deficiency of the Cockayne syndrome B (CSB) gene aggravates the genomic instability caused by endogenous oxidative DNA base damage in mice. Oncogene. 2007;26:4044-8 pubmed
    ..The data indicate that CSB is involved in the inhibition of mutations caused by spontaneous oxidative DNA base damage in a non-transcribed gene. ..
  6. Garssen J, van Steeg H, De Gruijl F, de Boer J, van der Horst G, van Kranen H, et al. Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and systemic immunosuppression. J Immunol. 2000;164:6199-205 pubmed
  7. Wijnhoven S, Kool H, Mullenders L, Slater R, van Zeeland A, Vrieling H. DMBA-induced toxic and mutagenic responses vary dramatically between NER-deficient Xpa, Xpc and Csb mice. Carcinogenesis. 2001;22:1099-106 pubmed
    ..These results indicate that both damage-induced cytotoxicity as well as intra-chromosomal recombinational events were not correlated to differences in cancer susceptibility in human NER syndrome patients. ..
  8. Griffin C, Waard H, Deans B, Thacker J. The involvement of key DNA repair pathways in the formation of chromosome rearrangements in embryonic stem cells. DNA Repair (Amst). 2005;4:1019-27 pubmed
    ..Strikingly, we found that loss of the Csb gene function specifically protects ES cells from complex exchanges, suggesting a role for transcription-associated events in complex exchange formation. ..
  9. Ling X, Zhang L, Huang Y, Bao W, Sun F. Neuronal ERCC6 mRNA expression in rat brain induced by a transient focal cerebral ischemia. Zhongguo Yao Li Xue Bao. 1999;20:15-20 pubmed
    To study whether the excision repair cross-complementing group 6 (ERCC6) is involved in the neuronal pathophysiological process following cerebral ischemia-reperfusion injury...
  10. Yin K, Sun F. Effect of dextromethorphan, a NMDA antagonist, on DNA repair in rat photochemical thrombotic cerebral ischemia. Brain Res. 1999;815:29-35 pubmed
    ..thrombotic ischemia model was used to study the possible roles of excision repair cross-complementing group 6 (ERCC6), a DNA repair gene, in the neuroprotection of dextromethorphan (DM), a NMDA antagonist, in ischemic brain injury...
  11. Nonnekens J, Pérez Fernández J, Theil A, Gadal O, Bonnart C, Giglia Mari G. Mutations in TFIIH causing trichothiodystrophy are responsible for defects in ribosomal RNA production and processing. Hum Mol Genet. 2013;22:2881-93 pubmed publisher
    ..Our findings provide evidence that defective ribosome synthesis represents a new faulty mechanism involved in the pathophysiology of TFIIH-related diseases. ..
  12. Okada K, Fujita T, Minamoto K, Liao H, Naka Y, Pinsky D. Potentiation of endogenous fibrinolysis and rescue from lung ischemia/reperfusion injury in interleukin (IL)-10-reconstituted IL-10 null mice. J Biol Chem. 2000;275:21468-76 pubmed
    ..Ischemia-driven IL-10 expression confers postischemic pulmonary protection by augmenting endogenous fibrinolytic mechanisms. ..
  13. Lin Z, Zhang X, Tuo J, Guo Y, Green B, Chan C, et al. A variant of the Cockayne syndrome B gene ERCC6 confers risk of lung cancer. Hum Mutat. 2008;29:113-22 pubmed
    Cockayne syndrome B protein (ERCC6) plays an essential role in DNA repair...
  14. Imam S, Indig F, Cheng W, Saxena S, Stevnsner T, Kufe D, et al. Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase. Nucleic Acids Res. 2007;35:4941-51 pubmed
    ..Activation of the c-Abl kinase in response to oxidative damage is not observed in CSB null cells. These results suggest that c-Abl and CSB may regulate each other in a reciprocal manner in response to oxidative stress. ..
  15. Baas D, Despriet D, Gorgels T, Bergeron Sawitzke J, Uitterlinden A, Hofman A, et al. The ERCC6 gene and age-related macular degeneration. PLoS ONE. 2010;5:e13786 pubmed publisher
    ..PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression...
  16. Matakidou A, El Galta R, Webb E, Rudd M, Bridle H, Eisen T, et al. Genetic variation in the DNA repair genes is predictive of outcome in lung cancer. Hum Mol Genet. 2007;16:2333-40 pubmed
    ..004); ERCC6 G399D (P = 0.023), ERCC6 Q1413R (P = 0.025), POLE (P = 0.014) and base excision repair: APEX1 D148E (P = 0...
  17. Selby C, Sancar A. Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase but is not a helicase and does not disrupt the ternary transcription complex of stalled RNA polymerase II. J Biol Chem. 1997;272:1885-90 pubmed
    ..Proteins encoded by the mfd gene in E. coli and by the ERCC6/CSB gene in humans, both of which possess the so-called helicase motifs, are required for the coupling reaction...
  18. Berg R, Rebel H, van der Horst G, van Kranen H, Mullenders L, van Vloten W, et al. Impact of global genome repair versus transcription-coupled repair on ultraviolet carcinogenesis in hairless mice. Cancer Res. 2000;60:2858-63 pubmed
    ..The relative cancer susceptibilities of GGR- and TCR-deficient skin could well depend on the balance between an increased mutation rate and the presence (in CSB -/-) or lack (in XPC -/-) of a compensatory apoptotic response. ..
  19. Falik Zaccai T, Laskar M, Kfir N, Nasser W, Slor H, Khayat M. Cockayne syndrome type II in a Druze isolate in Northern Israel in association with an insertion mutation in ERCC6. Am J Med Genet A. 2008;146A:1423-9 pubmed publisher (TCR) and a marked correction of the abnormal cellular phenotype with a plasmid containing the cDNA of the ERCC6 gene. Molecular studies led to identification of a novel insertion mutation, c...
  20. Jaakkola E, Mustonen A, Olsen P, Miettinen S, Savuoja T, Raams A, et al. ERCC6 founder mutation identified in Finnish patients with COFS syndrome. Clin Genet. 2010;78:541-7 pubmed publisher
    ..Two living and one of the deceased patients were all shown to possess a novel homozygous mutation in the ERCC6 [Cockayne syndrome B (CSB)] gene, thereby confirming the diagnosis on molecular genetic level even for the earlier ..
  21. Meira L, Graham J, Greenberg C, Busch D, Doughty A, Ziffer D, et al. Manitoba aboriginal kindred with original cerebro-oculo- facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene. Am J Hum Genet. 2000;66:1221-8 pubmed
    ..This mutation was also detected in three other patients with COFS syndrome from the Manitoba Aboriginal population group. These results suggest that CS and COFS syndrome share a common pathogenesis. ..
  22. Fousteri M, Vermeulen W, Van Zeeland A, Mullenders L. Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo. Mol Cell. 2006;23:471-82 pubmed
    ..These results give insight into the nature and order of molecular events that take place during TCR in the context of chromosomal DNA. ..
  23. Fritz G, Kaina B. Late activation of stress kinases (SAPK/JNK) by genotoxins requires the DNA repair proteins DNA-PKcs and CSB. Mol Biol Cell. 2006;17:851-61 pubmed
    ..The data show that sensing of DNA damage by DNA-PK(cs) and CSB causes a delayed SEK1/MKK4-mediated dual phosphorylation of SAPK/JNK. ..
  24. de Waard H, de Wit J, Andressoo J, van Oostrom C, Riis B, Weimann A, et al. Different effects of CSA and CSB deficiency on sensitivity to oxidative DNA damage. Mol Cell Biol. 2004;24:7941-8 pubmed
    ..We suggest that the CSA and CSB proteins in part perform separate roles in different DNA damage response pathways. ..
  25. Selby C, Sancar A. Cockayne syndrome group B protein enhances elongation by RNA polymerase II. Proc Natl Acad Sci U S A. 1997;94:11205-9 pubmed
    ..Thus a deficiency in transcription elongation may contribute to the CS phenotype...
  26. Fousteri M, Mullenders L. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects. Cell Res. 2008;18:73-84 pubmed publisher
    ..These and yet unidentified proteins will accomplish not only efficient repair of transcription-blocking lesions, but are also likely to contribute to DNA damage signalling events. ..
  27. Ma H, Hu Z, Wang H, Jin G, Wang Y, Sun W, et al. ERCC6/CSB gene polymorphisms and lung cancer risk. Cancer Lett. 2009;273:172-6 pubmed publisher
    ..Of them, Cockayne syndrome complementation group B (CSB), coded by ERCC6, recruits NER repair factors to the DNA damage site and plays an important role in the repair process...
  28. van Oosten M, Rebel H, Friedberg E, van Steeg H, van der Horst G, van Kranen H, et al. Differential role of transcription-coupled repair in UVB-induced G2 arrest and apoptosis in mouse epidermis. Proc Natl Acad Sci U S A. 2000;97:11268-73 pubmed
    ..G(2) arrest is manifest only under conditions of proficient TCR in combination with deficient GGR, indicating that epidermal cells become arrested in the G(2) phase as a result of persisting damage in their genome. ..
  29. Nagtegaal A, Rainey R, van der Pluijm I, Brandt R, van der Horst G, Borst J, et al. Cockayne syndrome group B (Csb) and group a (Csa) deficiencies predispose to hearing loss and cochlear hair cell degeneration in mice. J Neurosci. 2015;35:4280-6 pubmed publisher
    ..Our data indicate that the hearing loss observed in CS patients is reproduced in mouse models of this disease. We hypothesize that accumulating DNA damage, secondary to the loss of TCR, contributes to susceptibility to hearing loss. ..
  30. Sarker A, Tsutakawa S, Kostek S, Ng C, Shin D, Peris M, et al. Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome. Mol Cell. 2005;20:187-98 pubmed
    ..Together, these results implicate coordinated recognition of stalled transcription by XPG and CSB in TCR initiation and suggest that TFIIH-dependent remodeling of stalled RNAPII without release may be sufficient to allow repair...
  31. Kamileri I, Karakasilioti I, Garinis G. Nucleotide excision repair: new tricks with old bricks. Trends Genet. 2012;28:566-73 pubmed publisher
    ..Together, these findings add new pieces to the puzzle for understanding NER and the relevance of NER defects in development and disease. ..