Cockayne 症候群細胞の紫外線高感受性機構

概要

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Cockayne syndrome (CS) fibroblastic cells exhibited the hypersensitive responses to ultraviolet (UV)-induced cell killing and sister chromatid exchange (SCE) formation without any detectable defects in nucleotide-excision repair and postreplication repair. Only a characteristic abnormality in cells of several CS strains was a defective recovery of DNA synthesis after UV irradiation with relatively low doses which allowed the recovery in normal cells. In this connection the enzymecycling assay revealed a 20-40% reduction in cellular NAD level in several CS strains, but CS cells retained the normal activity of poly (ADP-ribose) synthesis. Using a typical CS strain of GM 739, exogenous supply of NAD effected the concentration-dependent, otherwise defective, recovery of post-UV DNA synthesis. This effect seemed specific to NAD, so far examined. Exogenous NAD also effected the partial normalization of hypersensitive UV-killing at 1 mM and the complete normalization of hyperinduction of SCE at a lower concentration of 0.1 mM. Such normalized phenomena occurred in the other CS strains used as well. We discussed the CS defect and its UV-hypersensitive mechanism, together with abnormal purine and thus NAD synthesis in the cells.
神戸大学の論文