The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

摘要: Patients with the genetic disease xeroderma pigmentosum (XP) lack capacity to carry out a specific type of DNA repair process called nucleotide excision (NER). The NER pathway plays critical role in damage resulting from ultraviolet (UV) radiation. A subset XP patients develops profound neurodegenerative condition known as neurological disease. Robbins and colleagues [Andrews A, Barrett S, J (1978) Xeroderma abnormalities correlate colony forming ability after irradiation. Proc Natl Acad Sci U S 75:1984-1988] hypothesized that since UV light cannot reach into human brain, results some form endogenous is normally repaired by pathway. In absence NER, accumulates, causing neuronal death blocking transcription. this manuscript, I consider evidence particular class oxidative lesions, 8,5'-cyclopurine-2'-deoxynucleosides, fulfills many criteria expected lesions XP. Specifically, these are chemically stable, but not any other process, strongly block transcription RNA polymerase II cells patients. similar set might be used evaluate candidate responsible for diseases defects mechanisms well.