Transcription increases the deletion frequency of long CTG center dot CAG triplet repeats from plasmids in Escherichia coli
Transcription increases the deletion frequency of long CTG center dot CAG triplet repeats from plasmids in Escherichia coli
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DOI：
10.1093/nar/25.14.2861
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发表时间：
1997-07-15
影响因子：
14.9
通讯作者：
Wells, RD
中科院分区：
文献类型：
--
作者：
Bowater, RP;Jaworski, A;Wells, RD
大肠杆菌中质粒上含有的长CTG.CAG重复序列的转录诱导显示出增加重复序列内缺失的频率。检测到这种升高的遗传不稳定性是因为转录成三联体重复序列的活性影响宿主细胞的生长转变，允许携带具有缺失的重复序列的质粒的细胞有利生长，在不同的培养物中观察到的缺失产物的多样性表明，转录以在重复序列中产生随机长度变化的方式改变了DNA的代谢。对于含有质粒而没有活性转录成三联体重复序列的培养物，或者那些保持指数生长的培养物，在重复序列内发生的缺失频率较低在这些孵育中，缺失的程度与细胞分裂的数量成比例，并且在每个培养物中观察到许多重复长度，这表明在长孵育时间下平均重复长度的降低是由于多个小缺失，这些观察结果表明，在大肠杆菌质粒上含有的长CTG、CAG重复序列的缺失。大肠杆菌的遗传不稳定性通过一种以上的途径发生，并且它们的遗传不稳定性水平被DNA上发生的酶促过程改变。
Induction of transcription into long CTG.CAG repeats contained on plasmids in Escherichia coli is shown to increase the frequency of deletions within the repeat sequences, This elevated genetic instability was detected because active transcription into the triplet repeat influenced the growth transitions of the host cell, allowing advantageous growth for cells harboring plasmids with deleted repeat sequences, The variety of deletion products observed in separate cultures suggests that transcription altered the metabolism of the DNA in a manner that produced random length changes in the repeat sequence, For cultures containing plasmids without active transcription into the triplet repeat, or those maintained in exponential growth, deletions occurred within the repeat at a lower frequency (5-20-fold lower), In these incubations the extent of deletions was proportional to the number of cell divisions and many repeat lengths were observed within each culture, suggesting that the decrease in average repeat length at long incubation times was due to multiple small deletions, These observations show that deletions within long CTG.CAG repeats contained on plasmids in E. coli occur via more than one pathway and their level of genetic instability is altered by the enzymatic processes occurring upon the DNA.