Gene expression in ataxia telangiectasia cells as perturbed by bleomycin treatment
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The autosomal recessive genetic disorder ataxia telangiectasia (AT) has been characterized in the RNA transcripts of cultured cells. Molecular species of poly (A) + RNA that are present in AT fibroblasts (ATFs) at levels different from those in normal human fibroblasts (NHFs) were cloned in the form of cDNAs. Treatment with bleomycin, which transiently inhibits DNA synthesis in NHFs but not in ATFs, differentiated ATFs and NHFs in the above cloning. Two cDNA clones with an identical DNA sequence were isolated, the corresponding RNA transcript of which was induced approximately twofold after bleomycin treatment in NHFs, but not in ATFs. The DNA sequence of these two cDNA clones, except for its polyadenylation part, was identical to the heavy-strand replication origin sequence of human mitochondrial DNA. The results indicate the possibility that the induction of this RNA transcript is involved in bleomycin-induced inhibition of DNA synthesis in normal human cells, while it is defective in AT cells. In addition, the previous observation that much fibronectin is produced in AT cells was confirmed in this study in terms of RNA transcription.
KeywordscDNA Clone Bleomycin Replication Origin Ataxia Telangiectasia Ataxia Telangiectasia
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