The mutational specificity of 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF2) in the lacI gene of Escherichia coli.

The mutational specificity of 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF2) in the lacI gene of Escherichia coli.
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大肠杆菌 lacI 基因中 2-(2-呋喃基)-3-(5-硝基-2-呋喃基)-丙烯酰胺 (AF2) 的突变特异性。

DOI:
10.1093/carcin/12.1.29
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发表时间:
1991
期刊:
影响因子:
4.7
通讯作者:
D. R. McCalla
D. R. McCalla
中科院分区:
医学2区
文献类型:
--
作者:
I. Lambert;T. A. Chin;D. W. Bryant;A. Gordon;B. Glickman;D. R. McCalla

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我们确定了大肠杆菌 lacI 基因中 5-硝基呋喃衍生物呋喃酰胺 (AF2) 的突变特异性。用 1 M AF2 处理 delta uvrB、pKM101 菌株产生的突变频率比未处理的对照高约 300 倍。通过DNA测序分析了165个AF2诱导的突变体,其中145个是碱基取代突变,11个是移码突变,其余的是小缺失、串联碱基取代和复杂突变。碱基取代主要发生在 G:C 碱基对上(大于 93%)。各种突变的比例与已报道的 AP 位点的比例非常相似。我们认为 AF2 诱变的主要机制是形成加合物,该加合物脱嘌呤产生 AP 位点,作为易错修复的底物。其中 72 个突变发生在 4 个 5'-TGC-3' 位点。大多数(10/11)移码突变发生在这样一个热点处,并且可能是通过从突变位点移除少于 100 bp 的反向重复序列来模板化的。
We have determined the mutational specificity of the 5-nitrofuran derivative furylfuramide (AF2) in the lacI gene of Escherichia coli. Treatment of a delta uvrB, pKM101 strain with 1 M AF2 yielded a mutation frequency approximately 300 times greater than that of untreated controls. Of the 165 AF2-induced mutants analysed by DNA sequencing, 145 were base substitution mutations, 11 were frameshifts, and the remainder small deletions, tandem base substitutions and complex mutations. Base substitution occurred primarily (greater than 93%) at G:C base pairs. The proportions of the various mutations are very similar to those that have been reported for AP sites. We suggest that the principal mechanism for AF2 mutagenesis is the formation of an adduct which depurinates to yield AP sites that serve as a substrate for error-prone repair. Seventy-two of the mutations occurred at four 5'-TGC-3' sites. The majority (10/11) of the frameshift mutations occurred at one such hotspot and could have been templated by an inverted repeat less than 100 bp removed from the site of the mutation.