Abstract
Four Cockayne's syndrome (CS) fibroblast strains with normal repair capacity were highly sensitive to ultraviolet (UV) killing due to the defective recovery of post-UV DNA synthesis. The enzymatic cycling assay for oxidized nicotinamide adenine dinucleotide (NAD +) revealed that CS cells had reduced levels of cellular NAD + pool. Exogenously supplied NAD + raised the cellular level in CS cells, and its concentrations of 0.5–1.0 mM almost normalized such a high UV lethality and defective post-UV DNA synthesis of CS cells. Highly elevated levels of UV-induced sisterchromatid exchanges in CS cells were also completely normalized with 0.1 mM NAD + in culture medium, but not in the xeroderma pigmentosum complementation group-A cells. However, the CS cells exhibited no obvious defect in the maximally deoxyribonuclase I-stimulated, intrinsic Poly(ADP-ribose) polymerase activity and the nearly normal time-course changes in the UV-induced activity of the enzyme, as assayed by the permeabilized cell system. Therefore, our data indicate that CS cells may have a partial deficiency in cellular NAD + level which results in insufficient or inadequate modifications of nuclear proteins and hence the defective recovery of post-UV DNA synthesis, so that exogenously supplied NAD + can rescue the defective phenomena as such in CS cells.
Published Version
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