ERCC8 gene
The ERCC8 gene provides instructions for making the CSA protein, which is essential for repairing damaged DNA within active genes.
Normal Function
The ERCC8 gene provides instructions for making a protein called Cockayne syndrome A (CSA), which 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, 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). The CSA protein interacts with other proteins, probably to identify areas of damaged DNA.
Health Conditions Related to Genetic Changes
Cockayne syndrome
Researchers have identified more than 30 ERCC8 gene mutations that can cause Cockayne syndrome. This rare condition includes a variety of features, including:
- An abnormally small head size (microcephaly)
- Very slow growth resulting in short stature
- Delayed development
- Increased sensitivity to sunlight (photosensitivity)
Some of the ERCC8 gene mutations result in the production of an abnormally short version of the CSA protein that cannot function properly. Other mutations change one of the building blocks (amino acids) used to make the CSA protein, which also results in a malfunctioning protein. The altered CSA protein probably disrupts DNA repair, leading to the accumulation of damaged DNA, which disrupts gene transcription and prevents the normal production of proteins. These abnormalities impair cell function and eventually lead to the death of cells in many organs and tissues.
UV-sensitive syndrome
At least one mutation in the ERCC8 gene can cause UV-sensitive syndrome, a condition characterized by unusual sensitivity to UV rays from the sun. People with this syndrome sunburn easily and have freckled skin or other changes in skin coloring (pigmentation). The known mutation replaces the amino acid tryptophan with the amino acid cysteine at position 361 in the CSA protein (written as Trp361Cys or W361C). This change prevents cells from repairing DNA damage caused by UV rays, and transcription of damaged genes is blocked.
Other Names for This Gene
- CKN1
- Cockayne syndrome 1 (classical)
- Cockayne syndrome 1 protein
- Cockayne syndrome, type A
- CSA
- ERCC8_HUMAN
- excision repair cross-complementation group 8
- excision repair cross-complementing rodent repair deficiency, complementation group 8