Relationship between pyrimidine dimers, 6-4 photoproducts, repair synthesis and cell survival: studies using cells from patients with trichothiodystrophy |
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Authors: | B C Broughton A R Lehmann S A Harcourt C F Arlett A Sarasin W J Kleijer F A Beemer R Nairn D L Mitchell |
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Institution: | MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton, Great Britain. |
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Abstract: | Trichothiodystrophy is a genetic disease which in the majority of cases studied is associated with a deficiency in the ability to repair UV damage in cellular DNA. Three categories of UV response have been identified. In type 1 the response is completely normal, whereas type 2 cells are deficient in excision-repair, with properties indistinguishable from those of XP complementation group D. Type 3 cells have normal survival following UV-irradiation and normal rates of removal of cyclobutane pyrimidine dimer sites. Nevertheless repair synthesis is reduced by 50% in these cell strains and this is associated with a marked reduction in the repair of 6-4 photoproducts from cellular DNA. The present results show that 50% or more of repair synthesis at early times after irradiation of normal primary human fibroblasts is attributable to repair of 6-4 products. They also suggest that repair of cyclobutane dimers is crucial for cell survival. |
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