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The official name of this gene is “excision repair cross-complementation group 8.”
ERCC8 is the gene's official symbol. The ERCC8 gene is also known by other names, listed below.
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.
The ERCC8 gene belongs to a family of genes called WDR (WD repeat domain containing).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
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, 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.
Cytogenetic Location: 5q12.1
Molecular Location on chromosome 5: base pairs 60,873,832 to 60,945,078
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 60,873,832 to base pair 60,945,078 on chromosome 5.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about ERCC8 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; amino acid ; cell ; cysteine ; deficiency ; DNA ; DNA damage ; DNA repair ; free radicals ; gene ; gene transcription ; mutation ; NER ; nucleotide ; nucleotide excision repair ; pigmentation ; protein ; radiation ; sensitivity ; sun sensitivity ; syndrome ; toxic ; transcription ; tryptophan ; UV rays
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.