IN-VITRO REPAIR OF OXIDATIVE DNA-DAMAGE BY HUMAN NUCLEOTIDE EXCISION-REPAIR SYSTEM - POSSIBLE EXPLANATION FOR NEURODEGENERATION IN XERODERMA-PIGMENTOSUM PATIENTS

Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers c aused by sunlight and, as a consequence, develop multiple cancers in a reas exposed to light, The second most common sign, present in 20-30% of XP patients, is a set of neurological abnormalities caused by neuro nal death in the central and peripheral nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so the cause of neurode generation in XP patients remains unexplained, In this study, we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol, are excised from DNA in vitro by the same enzyme system responsible f or removing pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP neurological disease may be caused by defective repai r of lesions that are produced in nerve cells by reactive oxygen speci es generated as by-products of an active oxidative metabolism.