title: Retroviral-mediated correction of DNA repair defect in xeroderma pigmentosum cells is associated with recovery of catalase activity.
abstract: Xeroderma pigmentosum (XP) is a rare inherited disease associated with photosensitivity, a very high susceptibility to develop neoplasm on sun-exposed skin and neurological abnormalities for some patients. We previously reported that diploid cell lines established from XP skin biopsies present an abnormal low level of catalase activity, which is involved in the defense against oxygen free radicals. This biochemical dysfunction, probably involved in the skin cancer formation, has been difficult to be directly related to the nucleotide excision repair (NER) defect in XP. In this paper we report that the retroviral-mediated transduction of XP diploid cells by the XPC and XPD/ERCC2 cDNAs fully and 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. These results imply that: (i) the reduced catalase activity in XP, which might 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.
authors.affiliation: Laboratory of Molecular Genetics, UPR 42 CNRS, Villejuif, France.
authors.forename: X
authors.initials: X
authors.lastname: Quilliet
authors.forename: O
authors.initials: O
authors.lastname: Chevallier-Lagente
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.forename: R
authors.initials: R
authors.lastname: Calvayrac
authors.forename: M
authors.initials: M
authors.lastname: Mezzina
authors.forename: A
authors.initials: A
authors.lastname: Sarasin
authors.forename: M
authors.initials: M
authors.lastname: Vuillaume
mesh_terms: D002374:Catalase / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005347:Fibroblasts; D005816:Genetic Complementation Test; D006801:Humans; D009249:NADP / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D014157:Transcription Factors; D014161:Transduction, Genetic; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000201:enzymology* / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011506:Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D009249:NADP; D004247:DNA; D002374:Catalase; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human