Cox R, Debenham P G, Masson W K, Webb M B
Mol Biol Med. 1986 Jun;3(3):229-44.
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.
利用以重组质粒为靶DNA的基因转移技术，研究了三种正常人类细胞系和一种对辐射敏感的毛细血管扩张性共济失调症（A-T）人类细胞系重新连接限制性内切酶诱导的双链（ds）DNA断裂的能力。以基因转移频率作为DNA重新连接的衡量指标进行的细胞实验结果有力地表明，A-T细胞系双链DNA断裂的错配修复频率大幅升高。对质粒转化细胞的DNA进行的Southern印迹分析证实了这一点，并进一步表明，A-T细胞系中的错配修复表现为断裂处或其周围的大片段缺失和/或重排。我们推测A-T细胞系中DNA末端重新连接和核酸外切酶消化之间的不平衡可能是错配修复的基础，并结合该疾病的主要临床特征讨论了这一机制。
