Repair of damage by ultraviolet radiation in xeroderma pigmentosum cell strains of complementation groups E and F |
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Authors: | B Zelle F Berends P H Lohman |
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Institution: | 1. Medical Biological Laboratory TNO, P.O. Box 45, 2280 AA Rijswijk The Netherlands;2. Dept. of Cell Biology and Genetics, Erasmus University, Rotterdam The Netherlands |
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Abstract: | The xeroderma pigmentosum fibroblast strains XP2RO, complementation group E, and XP23OS, group F, were compared with normal human primary fibroblasts with regard to repair of damage induced by 254-nm UV. In XP2RO cells, repair DNA synthesis, measured by autoradiography (unscheduled DNA synthesis = UDS), was about 50% of the value found in normal human cells. In these cells also the removal of UV-induced sites recognized by a specific UV-endonuclease proceeds at a reduced rate. By having BUdR incorporated into the repaired regions, followed by the induction of breaks in these patches by 313-nm UV, it was shown that the reduced repair synthesis is not caused by a shorter length of the repair regions in XP2RO, but is solely due to a reduction in the number of sites removed by excision repair. In XP23OS a discrepancy was observed between the level of UDS, which was about 10% of the normal value, and other repair-dependent properties such as UV survival, host-cell reactivation and removal of UV-endonuclease-susceptible sites, which were less reduced than could be expected from the UDS level. However, when UDS was followed over a longer period than the 2 or 3 h normally used in UDS analysis, it appeared that in XP23OS cells, the rate of UDS remained constant whereas the rate decreased in normal control cells. Consequently, the residual level of UDS varies with the period over which it is studied. |
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Keywords: | BUdR 5-bromodeoxyuridine HU hydroxyurea PBS phosphate-buffered saline TdR thymidine UDS unscheduled DNA synthesis UV ultraviolet radiation XP xeroderma pigmentosum |
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