RETROVIRAL-MEDIATED CORRECTION OF DNA-REPAIR DEFECT IN XERODERMA-PIGMENTOSUM CELLS IS ASSOCIATED WITH RECOVERY OF CATALASE ACTIVITY

Xeroderma pigmentosum (XP) is a rare inherited disease associated with photosensitivity, a very high susceptibility to develop neoplasm on s un-exposed skin and neurological abnormalities for some patients. We p reviously reported that diploid cell lines established from XP skin bi opsies present an abnormal low level of catalase activity, which is in volved in the defense against oxygen free radicals. This biochemical d ysfunction, probably involved in the skin cancer formation, has been d ifficult to be directly related to the nucleotide excision repair (NER ) defect in XP. In this paper we report that the retroviral-mediated t ransduction of XP diploid cells by the XPC and XPD/ERCC2 cDNAs fully a nd stably corrects the NER defect in terms of survival and unscheduled DNA synthesis (UDS) after ultraviolet (UV) irradiation. The catalase activity in transduced cells was recovered up to normal levels only in cells transduced with repair genes correcting the repair defect. Thes e results imply that: (i) the reduced catalase activity in XP, which m ight result from cellular depletion of its NADPH cofactor, is directly related to impaired DNA repair, and (ii) this depletion might be one of the multiple cellular consequences of XP inborn defect. (C) 1997 El sevier Science B.V.