Reviewed July 2012
What is the official name of the ERCC6 gene?
The official name of this gene is “excision repair cross-complementing rodent repair deficiency, complementation group 6.”
ERCC6 is the gene's official symbol. The ERCC6 gene is also known by other names, listed below.
What is the normal function of the ERCC6 gene?
The ERCC6 gene provides instructions for making a protein commonly called the Cockayne syndrome B (CSB) protein. This protein is involved in repairing damaged DNA and appears to assist with gene transcription, which is the first step in protein production. Although the role of the CSB protein is not clearly understood, this protein might help to start (initiate) gene transcription and then monitor its progress.
DNA can be damaged by ultraviolet (UV) rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals. If left uncorrected, DNA damage accumulates, which causes cells to malfunction and can lead to cell death. Although DNA damage occurs frequently, normal cells are usually able to fix it before it can cause problems. Cells have several mechanisms to correct DNA damage; one such mechanism involves the CSB protein. This protein specializes in repairing damaged DNA within active genes (those genes undergoing gene transcription). When DNA in active genes is damaged, the enzyme that carries out gene transcription (RNA polymerase) gets stuck, and the process stalls. Researchers think that the CSB protein helps remove RNA polymerase from the damaged site, so the DNA can be repaired. The CSB protein may also assist in restarting gene transcription after the damage is corrected.
How are changes in the ERCC6 gene related to health conditions?
- Cockayne syndrome - caused by mutations in the ERCC6 gene
More than 60 ERCC6 gene mutations that cause Cockayne syndrome have been identified. Many of these mutations lead to the production of an abnormally short version of the CSB protein that cannot function properly. Other mutations change one of the building blocks (amino acids) used to make the CSB protein, which also results in a malfunctioning protein.
It is unclear how ERCC6 gene mutations lead to Cockayne syndrome. The altered CSB protein probably hinders DNA repair and may be unable to assist with gene transcription. As a result, damaged DNA is not fixed, and gene transcription may be disrupted. These abnormalities impair cell function and eventually lead to the death of cells in many organs and tissues. The increased cell death likely contributes to features of Cockayne syndrome, such as growth failure and premature aging.
- UV-sensitive syndrome - caused by mutations in the ERCC6 gene
UV-sensitive syndrome, which is a disorder characterized by sun sensitivity, can also result from mutations in the ERCC6 gene. People with this condition sunburn easily and have freckled skin or other changes in skin coloring (pigmentation). At least one ERCC6 gene mutation has been found to cause UV-sensitive syndrome. This mutation, which is written as Arg77Ter or R77X, replaces the amino acid arginine with a premature stop signal at position 77 in the CSB protein. If any protein is produced, it is abnormally short and quickly broken down. Without this protein, skin cells cannot repair DNA damage caused by UV rays, and transcription of damaged genes is blocked. However, it is unclear exactly how a loss of the CSB protein causes UV-sensitive syndrome.
Where is the ERCC6 gene located?
Cytogenetic Location: 10q11.23
Molecular Location on chromosome 10: base pairs 50,662,525 to 50,747,168
The ERCC6 gene is located on the long (q) arm of chromosome 10 at position 11.23.
More precisely, the ERCC6 gene is located from base pair 50,662,525 to base pair 50,747,168 on chromosome 10.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about ERCC6?
You and your healthcare professional may find the following resources about ERCC6 helpful.
Educational resources - Information pages
- Molecular Biology of the Cell (fourth edition, 2002): DNA Repair (http://www.ncbi.nlm.nih.gov/books/NBK26879/)
- National Institutes of Health: What is DNA repair? (http://www.nih.gov/sigs/dna-rep/whatis.html)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1342/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for ERCC6 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=2074%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(ERCC6%5BTIAB%5D)%20OR%20(CSB%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/609413)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/CSBID302.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=2074)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=3438)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2074)
What other names do people use for the ERCC6 gene or gene products?
- Rad26 (yeast) homolog
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding ERCC6?
amino acid ;
base excision repair ;
chromatin remodeling ;
DNA damage ;
DNA repair ;
free radicals ;
gene transcription ;
macular degeneration ;
nucleotide excision repair ;
RNA polymerase ;
sun sensitivity ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Beerens N, Hoeijmakers JH, Kanaar R, Vermeulen W, Wyman C. The CSB protein actively wraps DNA. J Biol Chem. 2005 Feb 11;280(6):4722-9. Epub 2004 Nov 16. (http://www.ncbi.nlm.nih.gov/pubmed/15548521?dopt=Abstract)
- Colella S, Nardo T, Botta E, Lehmann AR, Stefanini M. Identical mutations in the CSB gene associated with either Cockayne syndrome or the DeSanctis-cacchione variant of xeroderma pigmentosum. Hum Mol Genet. 2000 May 1;9(8):1171-5. (http://www.ncbi.nlm.nih.gov/pubmed/10767341?dopt=Abstract)
- Colella S, Nardo T, Mallery D, Borrone C, Ricci R, Ruffa G, Lehmann AR, Stefanini M. Alterations in the CSB gene in three Italian patients with the severe form of Cockayne syndrome (CS) but without clinical photosensitivity. Hum Mol Genet. 1999 May;8(5):935-41. (http://www.ncbi.nlm.nih.gov/pubmed/10196384?dopt=Abstract)
- Greenhaw GA, Hebert A, Duke-Woodside ME, Butler IJ, Hecht JT, Cleaver JE, Thomas GH, Horton WA. Xeroderma pigmentosum and Cockayne syndrome: overlapping clinical and biochemical phenotypes. Am J Hum Genet. 1992 Apr;50(4):677-89. (http://www.ncbi.nlm.nih.gov/pubmed/1372469?dopt=Abstract)
- Horibata K, Iwamoto Y, Kuraoka I, Jaspers NG, Kurimasa A, Oshimura M, Ichihashi M, Tanaka K. Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome. Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15410-5. Epub 2004 Oct 14. (http://www.ncbi.nlm.nih.gov/pubmed/15486090?dopt=Abstract)
- Lainé JP, Egly JM. When transcription and repair meet: a complex system. Trends Genet. 2006 Aug;22(8):430-6. Epub 2006 Jun 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16797777?dopt=Abstract)
- Laugel V, Dalloz C, Durand M, Sauvanaud F, Kristensen U, Vincent MC, Pasquier L, Odent S, Cormier-Daire V, Gener B, Tobias ES, Tolmie JL, Martin-Coignard D, Drouin-Garraud V, Heron D, Journel H, Raffo E, Vigneron J, Lyonnet S, Murday V, Gubser-Mercati D, Funalot B, Brueton L, Sanchez Del Pozo J, Muñoz E, Gennery AR, Salih M, Noruzinia M, Prescott K, Ramos L, Stark Z, Fieggen K, Chabrol B, Sarda P, Edery P, Bloch-Zupan A, Fawcett H, Pham D, Egly JM, Lehmann AR, Sarasin A, Dollfus H. Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Hum Mutat. 2010 Feb;31(2):113-26. doi: 10.1002/humu.21154. (http://www.ncbi.nlm.nih.gov/pubmed/19894250?dopt=Abstract)
- Licht CL, Stevnsner T, Bohr VA. Cockayne syndrome group B cellular and biochemical functions. Am J Hum Genet. 2003 Dec;73(6):1217-39. Epub 2003 Nov 24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14639525?dopt=Abstract)
- Mallery DL, Tanganelli B, Colella S, Steingrimsdottir H, van Gool AJ, Troelstra C, Stefanini M, Lehmann AR. Molecular analysis of mutations in the CSB (ERCC6) gene in patients with Cockayne syndrome. Am J Hum Genet. 1998 Jan;62(1):77-85. Erratum in: Am J Hum Genet 1999 May;64(5):1491. (http://www.ncbi.nlm.nih.gov/pubmed/9443879?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2074)
- Newman JC, Bailey AD, Weiner AM. Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling. Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9613-8. Epub 2006 Jun 13. (http://www.ncbi.nlm.nih.gov/pubmed/16772382?dopt=Abstract)
- Proietti-De-Santis L, Drané P, Egly JM. Cockayne syndrome B protein regulates the transcriptional program after UV irradiation. EMBO J. 2006 May 3;25(9):1915-23. Epub 2006 Apr 6. (http://www.ncbi.nlm.nih.gov/pubmed/16601682?dopt=Abstract)
- Spivak G, Hanawalt PC. Host cell reactivation of plasmids containing oxidative DNA lesions is defective in Cockayne syndrome but normal in UV-sensitive syndrome fibroblasts. DNA Repair (Amst). 2006 Jan 5;5(1):13-22. Epub 2005 Aug 29. (http://www.ncbi.nlm.nih.gov/pubmed/16129663?dopt=Abstract)
- van den Boom V, Citterio E, Hoogstraten D, Zotter A, Egly JM, van Cappellen WA, Hoeijmakers JH, Houtsmuller AB, Vermeulen W. DNA damage stabilizes interaction of CSB with the transcription elongation machinery. J Cell Biol. 2004 Jul 5;166(1):27-36. Epub 2004 Jun 28. (http://www.ncbi.nlm.nih.gov/pubmed/15226310?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.