Ataxia-telangiectasia: a human mutation giving high-frequency misrepair of DNA double-stranded scissions.
The ability of three normal and one radiosensitive Ataxia-telangiectasia (A-T) human cell lines to rejoin restriction endonuclease-induced double-stranded (ds) DNA scissions was investigated using gene-transfer techniques with recombinant plasmid as target DNA. The results of cellular experiments using gene transfer frequencies as a measure of DNA rejoining strongly suggested that the A-T cell line had a greatly elevated frequency of misrepair of double-stranded DNA scissions. Southern blot analysis of DNA from plasmid-transformed cells confirmed this and further suggested that the misrepair in the A-T cell line took the form of large deletions and/or rearrangements at or around the scission. We postulate a disequilibrium in A-T between rejoining and exonuclease digestion of DNA termini as a possible basis for the misrepair and discuss this mechanism in relation to the major clinical features of the disease.
D001260:Ataxia Telangiectasia / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D004260:DNA Repair; D004262:DNA Restriction Enzymes; D006801:Humans; D009154:Mutation; D010957:Plasmids; D014162:Transfection; D014170:Transformation, Genetic
D004262:DNA Restriction Enzymes