FAILURE OF RNA-SYNTHESIS TO RECOVER AFTER UV IRRADIATION - AN EARLY DEFECT IN CELLS FROM INDIVIDUALS WITH COCKAYNES SYNDROME AND XERODERMA PIGMENTOSUM

Abstract

Previous work has shown that in cells from the UV sensitive genetic disorder. Cockayne''s syndrome, DNA synthesis fails to recover after UV irradiation despite the fact that these cells have no detectable defect in either excision or daughter-strand repair pathways. Cockayne cells and cells from a number of patients with xeroderma pigmentosum are sensitive to the lethal effects of UV irradiation in stationary phase under conditions in which no DNA is synthesized after irradiation. In normal and defective human fibroblasts, RNA synthesis is depressed after UV irradiation. In normal (dividing) cells RNA synthesis recovers very rapidly, but this recovery does not occur in Cockayne cells, and it is reduced or absent in xeroderma pigmentosum cells from different complementation groups. Qualitatively similar results are obtained with cells in stationary phase. The recovery of RNA synthesis in the various defective cell strains is not correlated with the overall extent of excision repair, but there is some correlation between recovery of RNA synthesis and cell survival after UV irradiation. These results implicate recovery of RNA synthesis as an important early response to UV irradiation.