Reviewed July 2012
What is the official name of the ERCC8 gene?
The official name of this gene is “excision repair cross-complementing rodent repair deficiency, complementation group 8.”
ERCC8 is the gene's official symbol. The ERCC8 gene is also known by other names, listed below.
What is the normal function of the ERCC8 gene?
The ERCC8 gene provides instructions for making a protein commonly called the Cockayne syndrome A (CSA) protein. Little is known about the function of this protein, although it is involved in repairing damaged DNA. DNA can be damaged by ultraviolet (UV) rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals. The damage caused by these agents can block vital cell activities such as gene transcription, which is the first step in protein production. 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 CSA protein. This protein specializes in repairing damaged DNA within active genes (those genes undergoing gene transcription). However, its specific role in this process is unclear. The CSA protein interacts with other proteins, probably to identify areas of damaged DNA.
How are changes in the ERCC8 gene related to health conditions?
- Cockayne syndrome - caused by mutations in the ERCC8 gene
Researchers have identified more than 25 ERCC8 gene mutations that can cause Cockayne syndrome. Many of these mutations result in the production of an abnormally short version of the CSA protein. Other mutations change one of the building blocks (amino acids) used to make the CSA protein, which also results in a malfunctioning protein.
It is unclear how ERCC8 gene mutations lead to Cockayne syndrome. The altered CSA protein probably disrupts DNA repair, which allows abnormalities to accumulate in DNA. 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 ERCC8 gene
UV-sensitive syndrome, which is a disorder characterized by sun sensitivity, can also result from mutations in the ERCC8 gene. People with this condition sunburn easily and have freckled skin or other changes in skin coloring (pigmentation). At least one ERCC8 gene mutation has been found to cause UV-sensitive syndrome. This mutation replaces the amino acid tryptophan with the amino acid cysteine at position 361 in the CSA protein (written as Trp361Cys or W361C). Although the effect of this change on the function of the protein is unknown, affected skin cells cannot repair DNA damage caused by UV rays, and consequently, transcription of damaged genes is blocked. It is unclear exactly how an abnormal CSA protein causes the signs and symptoms of UV-sensitive syndrome.
Where is the ERCC8 gene located?
Cytogenetic Location: 5q12.1
Molecular Location on chromosome 5: base pairs 60,169,658 to 60,240,904
The ERCC8 gene is located on the long (q) arm of chromosome 5 at position 12.1.
More precisely, the ERCC8 gene is located from base pair 60,169,658 to base pair 60,240,904 on chromosome 5.
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 ERCC8?
You and your healthcare professional may find the following resources about ERCC8 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 ERCC8 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=1161%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=((ERCC8%5BTIAB%5D)%20OR%20(CKN1))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/609412)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/CSAID301.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/1161)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=1161)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=3439)
- Human DNA Repair Genes (http://sciencepark.mdanderson.org/labs/wood/DNA_Repair_Genes.html)
What other names do people use for the ERCC8 gene or gene products?
- Cockayne syndrome 1 (classical)
- Cockayne syndrome 1 protein
- Cockayne syndrome, type A
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 ERCC8?
amino acid ;
DNA damage ;
DNA repair ;
free radicals ;
gene transcription ;
nucleotide excision repair ;
sun sensitivity ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Bertola DR, Cao H, Albano LM, Oliveira DP, Kok F, Marques-Dias MJ, Kim CA, Hegele RA. Cockayne syndrome type A: novel mutations in eight typical patients. J Hum Genet. 2006;51(8):701-5. Epub 2006 Jul 25. (http://www.ncbi.nlm.nih.gov/pubmed/16865293?dopt=Abstract)
- Cao H, Williams C, Carter M, Hegele RA. CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism. J Hum Genet. 2004;49(1):61-3. Epub 2003 Dec 6. (http://www.ncbi.nlm.nih.gov/pubmed/14661080?dopt=Abstract)
- Dubaele S, Egly JM. Cockayne syndrome, between transcription and DNA repair defects. J Eur Acad Dermatol Venereol. 2002 May;16(3):220-6. (http://www.ncbi.nlm.nih.gov/pubmed/12195559?dopt=Abstract)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/1161)
- Kamiuchi S, Saijo M, Citterio E, de Jager M, Hoeijmakers JH, Tanaka K. Translocation of Cockayne syndrome group A protein to the nuclear matrix: possible relevance to transcription-coupled DNA repair. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):201-6. (http://www.ncbi.nlm.nih.gov/pubmed/11782547?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)
- Nardo T, Oneda R, Spivak G, Vaz B, Mortier L, Thomas P, Orioli D, Laugel V, Stary A, Hanawalt PC, Sarasin A, Stefanini M. A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6209-14. doi: 10.1073/pnas.0902113106. Epub 2009 Mar 27. (http://www.ncbi.nlm.nih.gov/pubmed/19329487?dopt=Abstract)
- Ridley AJ, Colley J, Wynford-Thomas D, Jones CJ. Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects. J Hum Genet. 2005;50(3):151-4. Epub 2005 Mar 3. (http://www.ncbi.nlm.nih.gov/pubmed/15744458?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 Hoffen A, Balajee AS, van Zeeland AA, Mullenders LH. Nucleotide excision repair and its interplay with transcription. Toxicology. 2003 Nov 15;193(1-2):79-90. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14599769?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.