XP is caused by a defect in the ability of cells to repair damage induced in DNA by ultraviolet light. This process (Nucleotide excision repair – NER) is a multi-step pathway, whereby the damage is recognised and subsequently cut out of the DNA. The resulting gap is then repaired (repair synthesis). Eight XP genes have been identified, of which XPE is one. The XPE protein is involved in recognition of the DNA damage, but it is not absolutely required, so unrepaired damage accumulates relatively slowly. All kinds of mutations have been identified in XPE patients. When NER is not functional, because of mutations in one of the XP genes, damage remains in DNA in exposed areas of the skin and the skin hypersensitivity results. Clinical diagnosis can be confirmed, either by molecular analysis of the XP genes and/or by analysing NER in cultured skin fibroblasts. This is commonly done by measuring the repair synthesis step of NER using a technique known as Unscheduled DNA Synthesis. In contrast to most of the other XP groups, repair in XPE is reduced only by 50%, whereas it is reduced by 70-100% in other groups.
XPE