Large deletions and untargeted substitutions induced by abasic site analog on leading versus lagging strand templates in human cells
Large deletions and untargeted substitutions induced by abasic site analog on leading versus lagging strand templates in human cells
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DOI：
10.1093/mutage/gez034
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发表时间：
2019-09-01
期刊：
影响因子：
2.7
通讯作者：
Kamiya, Hiroyuki
中科院分区：
文献类型：
--
作者：
Suzuki, Tetsuya;Katayama, Yuri;Kamiya, Hiroyuki
四氢呋喃型脱碱基位点类似物（THF）会在人体细胞中诱导大的缺失突变。为了比较THF在前导链和滞后链模板上诱导的大缺失，将在supF基因外特定位置带有类似物的质粒DNA引入人U2OS细胞中。将从转染细胞中回收的复制DNA电穿孔至大肠杆菌指示菌株中。滞后链模板上的 THF 比前导链模板上的 THF 产生更多的 suF 突变体。这种不平等的致突变性不仅是由于基因中诱导的大缺失和非目标碱基取代的频率较高。这些结果表明，当滞后链模板上形成脱碱基位点时，两种类型的突变都会更频繁地发生。
The tetrahydrofuran-type abasic site analog (THF) induces large deletion mutations in human cells. To compare the large deletions induced by THF on leading and lagging strand templates, plasmid DNAs bearing the analog at a specific position outside the supF gene were introduced into human U2OS cells. The replicated DNAs recovered from the transfected cells were electroporated into an Escherichia coli indicator strain. THF on the lagging strand template produced more supF mutants than THF on the leading strand template. This unequal mutagenicity was due to the higher frequencies of not only large deletions but also untargeted base substitutions induced in the gene. These results suggested that both types of mutations occur more frequently when abasic sites are formed on the lagging strand template.