Bleomycin-resistant DNA synthesis in ataxia telangiectasia cells

Abstract

Ataxia telangiectasia (AT) is a human autosomal recessive disease that exhibits (in addition to the symptoms implied by its name) immune deficiencies, greatly increased risk of lymphoreticular cancer and unusual sensitivity to ionizing radiation (see ref. 1 for review). Although cells from AT patients are abnormally sensitive to killing by X-ray irradiation, DNA synthesis in AT cells is resistant to such treatment^2,3. This resistance is primarily due to less inhibition of replicon initiation in AT cells than in normal cells, but there is also less inhibition of chain elongation in AT cells³. We now report that DNA synthesis in AT cells is also resistant to DNA damage induced by bleomycin but not to damage induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) or actinomycin D. Of these agents, only X rays and bleomycin directly cause DNA strand breaks, indicating that AT cells are defective in the system that in normal cells prolongs the time during which strand breaks can be repaired, replicon initiation inhibited and the chromatin structure returned to its normal state.