DNA lesions such as 8,5′-cyclopurine-2′-deoxynucleosides (cyclopurines) accumulate in XP neurons.4,52-54 These are likely candidates as causative agents of neurodegeneration in XP since cyclopurines are lesions that can only be repaired through NER, they are endogenously produced, chemically stable and they may block transcription processes.52 In brain tissue of XPA knockout mice (Xpa−/−), cyclopurines accumulated at a faster rate compared to wild-type animals.53 A role for mitochondrial dysfunction has also been proposed in recent studies. This evidence concerns the gene XPA and xeroderma pigmentosum.