Fix D F, Glickman B W
Biology Department, York University, Ontario, Canada.
Mol Gen Genet. 1987 Aug;209(1):78-82. doi: 10.1007/BF00329839.
A collection of 164 spontaneous lacI- mutations were recovered from a uracil-DNA glycosylase deficient (Ung-) strain of Escherichia coli and analyzed by DNA sequencing. As predicted by genetic studies, G:C----A:T transitions predominated among base substitution events. However, DNA sequence analysis indicated that these events did not occur at random. Of the 31 G:C----A:T transitions recovered, 24 involved cytosine residues located in the nontranscribed strand of the gene and 15 of the 31 transitions occurred at cytosines located on the 3' side of 3 or more A:T base pairs. These differentials likely reflect the more single-stranded character of the non-transcribed strand of the gene and of regions rich in A:T base pairs. In addition, mutation at the frameshift hotspot was altered in the Ung- strain, suggesting a role for DNA repair in the formation of structural intermediates that potentiate these events. Also, the analysis of non-hotspot frameshifts, deletions and duplications showed that many involved local DNA sequence. Specifically, several of the frameshift, deletion and duplication mutations occurred near the sequence 5'-CTGG-3'. Thus, DNA sequence analysis of mutational specificity in an Ung- strain has provided evidence that gene expression, DNA repair and DNA context can all potentially influence the classes and frequencies of spontaneous mutation.
从一株尿嘧啶-DNA糖基化酶缺陷型（Ung-）大肠杆菌中分离出164个自发的lacI-突变体，并进行DNA测序分析。正如遗传学研究所预测的那样，在碱基替换事件中，G:C→A:T转换占主导地位。然而，DNA序列分析表明这些事件并非随机发生。在检测到的31个G:C→A:T转换中，24个涉及基因非转录链上的胞嘧啶残基，且其中15个转换发生在3个或更多A:T碱基对3'端的胞嘧啶上。这些差异可能反映了基因非转录链以及富含A:T碱基对区域更多的单链特征。此外，Ung-菌株中移码热点处的突变发生了改变，这表明DNA修复在增强这些事件的结构中间体形成过程中发挥了作用。同样，对非热点移码、缺失和重复的分析表明，许多都涉及局部DNA序列。具体而言，一些移码、缺失和重复突变发生在5'-CTGG-3'序列附近。因此，对Ung-菌株中突变特异性的DNA序列分析提供了证据，表明基因表达、DNA修复和DNA环境都可能潜在地影响自发突变的类型和频率。
