title: Electroporation of normal human DNA endonucleases into xeroderma pigmentosum cells corrects their DNA repair defect.
abstract: Cells from patients with the cancer-prone inherited disease, xeroderma pigmentosum (XP) are known to be defective in the endonuclease-mediated incision step in excision repair of a number of different types of DNA adducts, but the molecular events responsible have not been delineated. We have previously reported isolation of two DNA endonucleases, pI 4.6 and 7.6, from normal human chromatin which recognize adducts produced by psoralen plus long wavelength ultraviolet radiation (UVA). These endonucleases are both present in XP complementation group A (XPA) cells even though these cells are hypersensitive to this type of damage. We now report that introduction by electroporation of either normal endonuclease into XPA cells restored their markedly deficient DNA repair-related unscheduled DNA synthesis (UDS) to higher than normal levels following exposure to psoralen plus UVA. Introduction of XPA endonucleases into similarly treated XPA cells had little or no restorative effect on UDS. However, both normal and XPA endonucleases increased UDS in normal cells to higher than normal levels. These results indicate that XPA cells have endonucleases which can repair these adducts but which cannot function in intact cells unless a factor(s), which they lack is provided by normal cells.
authors.affiliation: Department of Pathology, UMDNJ, New Jersey Medical School, Newark.
authors.forename: G J
authors.initials: GJ
authors.lastname: Tsongalis
authors.forename: W C
authors.initials: WC
authors.lastname: Lambert
authors.forename: M W
authors.initials: MW
authors.lastname: Lambert
mesh_terms: D004260:DNA Repair; D003850:Deoxyribonuclease I / Q000502:physiology*; D005816:Genetic Complementation Test; D006801:Humans; D011701:PUVA Therapy; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000235:genetics*
chemical_list: D003850:Deoxyribonuclease I