ERCC8

The ERCC8 gene provides instructions for making a protein commonly called Cockayne syndrome A (CSA) protein. Little is known about the exact function of this protein, but it helps cells recover when DNA is damaged. DNA can be damaged by several agents such as toxic compounds and ultraviolet (UV) rays from sunlight. The damage caused by these agents can block vital cell activities such as making a blueprint of a gene (through a process called transcription), which is a required step for protein production. If left uncorrected, DNA damage accumulates, eventually causing cell death. Normally, however, cells use several repair mechanisms to correct DNA damage before cell activities are impaired. One such mechanism involves the CSA protein. This protein specializes in repairing damaged DNA within active genes (those genes undergoing transcription), but its specific role is unclear. It is known to interact with other proteins, probably to identify areas of damaged DNA.

Cockayne syndrome - caused by mutations in the ERCC8 gene

Researchers have identified several ERCC8 mutations that cause Cockayne syndrome. More than half of the reported mutations result in a shortened version of the CSA protein. The remaining mutations change one of the building blocks (amino acids) used to make the CSA protein. As a result of these mutations, the CSA protein cannot function properly, and damaged DNA in active genes is not rapidly repaired. The accumulated DNA damage is assumed to cause impaired cell function and eventually, the death of cells in many organs. Increased cell death probably contributes to features of Cockayne syndrome such as growth failure and premature aging.