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Length of CTG center dot CAG repeats determines the influence of mismatch repair on genetic instability

机译:CTG中心点CAG重复的长度决定了错配修复对遗传不稳定的影响

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We showed previously that mutations in methyl-directed mismatch repair of Esrherichia coli reduced the occurrence of large deletions in (CTG.CAG)(175) repeats contained on plasmids. By contrast, other workers reported that mutations in mismatch repair increase the frequency of small-length changes in the shorter (CTG.CAG)(64). Using plasmids with a variety of lengths and purity of(CTG.CAG) repeats, we have resolved these apparently conflicting observations. We show that all lengths of (CTG.CAG) repeats are subject to small-length changes (eight repeats) in (CTG.CAG)(n) occur more readily in cells with active mismatch repair. The frequency of large deletions is proportional to the tract length; in our assays they become prominent in tracts greater than 100 repeats. Interruptions in repeat purity enhance the occurrence of large deletions. In addition, we observed a high level of incidence of deletions in (CTG.CAG) repeats for cultures passing repeatedly through stationary phase during long-term growth experiments of all strains (i.e. with active or inactive mismatch repair). These results agree with current theories on mismatch repair acting on DNA slippage events that occur in DNA triplet-repeats. (C) 2000 Academic Press. [References: 36]
机译:我们以前表明,在大肠杆菌的甲基定向错配修复中的突变减少了质粒上包含的(CTG.CAG)(175)重复序列中大缺失的发生。相比之下,其他工人报告说,错配修复中的突变会增加较短的小长度突变的频率(CTG.CAG)(64)。使用具有各种长度和纯度的(CTG.CAG)重复序列的质粒,我们已经解决了这些明显矛盾的观察。我们显示,失配修复途径失活后,所有长度的(CTG.CAG)重复序列都会发生小长度变化(<八个重复序列)。然而,在具有主动错配修复的细胞中,(CTG.CAG)(n)中的大缺失(> 8个重复)更容易发生。大量缺失的频率与导管长度成正比。在我们的测定中,它们在超过100次重复的片段中变得突出。重复纯度的中断会增加大缺失的发生。此外,我们观察到在所有菌株的长期生长实验(即具有主动或非主动错配修复)中反复通过固定相的培养物中,(CTG.CAG)重复序列中缺失的发生率很高。这些结果与有关错配修复作用的现行理论相一致,错配修复作用于DNA三联体重复中发生的DNA滑动事件。 (C)2000学术出版社。 [参考:36]

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