Schumacher S, Pinet I, Bichara M
Cancérogénèse et Mutagénèse Moléculaire et Structurale UPR 9003, CNRS, Pôle API, Boulevard Sébastien Brant, 67400 Strasbourg-Illkirch, France.
J Mol Biol. 2001 Mar 16;307(1):39-49. doi: 10.1006/jmbi.2000.4489.
Many human hereditary disease genes are associated with the expansion of triplet repeat sequences. In Escherichia coli (CTG/CAG) triplet repeat sequences are unstable and we have developed a plasmid-based assay enabling us to observe and quantify both expansions and deletions. In this work, we have investigated the role of transcription on the instability of a (CTG/CAG) insert containing 64 repeats. Using this assay, we show that induction of transcription results in a significant increase in the frequency of long deletions and a reduction in the frequency of long expansions. On the other hand, overproduction of transcription repressor molecules leads to an increase in both expansions and deletions. In this latter case, we propose that the increased instability is due to the arrest of replication progression by the interaction of the repressor molecule with its cognate operator and subsequent generations of DNA strand breaks.
许多人类遗传疾病基因与三联体重复序列的扩增有关。在大肠杆菌中，（CTG/CAG）三联体重复序列不稳定，我们开发了一种基于质粒的检测方法，使我们能够观察和量化扩增和缺失情况。在这项工作中，我们研究了转录对含有64个重复序列的（CTG/CAG）插入片段不稳定性的作用。使用该检测方法，我们发现转录的诱导导致长片段缺失频率显著增加，长片段扩增频率降低。另一方面，转录阻遏分子的过量产生导致扩增和缺失均增加。在后一种情况下，我们认为不稳定性增加是由于阻遏分子与其同源操纵子相互作用导致复制进程停滞以及随后产生的DNA链断裂所致。
