Kang S, Ohshima K, Jaworski A, Wells R D
Department of Biochemistry and Biophysics, Texas A&M University Texas Medical Center, Houston 77030-3303, USA.
J Mol Biol. 1996 May 17;258(4):543-7. doi: 10.1006/jmbi.1996.0266.
The expansion and contraction of CTG and CGG trinucleotide repeat sequences have been associated with several heritable genetic diseases. We developed a system for investigating the expansion of triplet repeat sequences in Escherichia coli in order to elucidate molecular mechanisms. Analysis of expanded regions using the interrupting CTA triplet sequence as a location marker within the CTG tract revealed that the expansion of large CTG repeats is one event rather than an accumulation of multiple small expansions and that the expansions occur more frequently in the region distal from the replication origin. Also, we showed that a loss of interruptions increases the expansion frequency. Thus, the instability of large triplet repeats in hereditary diseases occurs by a mechanism different from the instability in microsatellite sequences caused by defects in mismatch repair systems for certain sporadic cancers and hereditary non-polyposis colorectal cancers.
CTG和CGG三核苷酸重复序列的扩增与收缩已与多种遗传性疾病相关联。我们开发了一种用于研究大肠杆菌中三联体重复序列扩增的系统，以阐明分子机制。使用中断的CTA三联体序列作为CTG区域内的定位标记对扩增区域进行分析，结果表明，大型CTG重复序列的扩增是一个事件，而非多个小扩增的积累，并且扩增在远离复制起点的区域更频繁地发生。此外，我们还表明中断的缺失会增加扩增频率。因此，遗传性疾病中大型三联体重复序列的不稳定性是通过一种不同于某些散发性癌症和遗传性非息肉病性结直肠癌错配修复系统缺陷所导致的微卫星序列不稳定性的机制发生的。
