i-Motif formation and spontaneous deletions in human cells.
i-Motif formation and spontaneous deletions in human cells.
复制标题
DOI：
10.1093/nar/gkac158
复制
发表时间：
2022-04-08
影响因子：
14.9
通讯作者：
Smith SS
中科院分区：
文献类型：
--
作者：
Martella M;Pichiorri F;Chikhale RV;Abdelhamid MAS;Waller ZAE;Smith SS
首先通过其与RACK 7基因座处的缺失的关联而检测到的d（TCCC）的串联体在整个人类基因组中广泛存在。圆二色光谱表明，当n > 3时，d（GGGA）n序列形成G-四链体，而当n ≥ 7时，d（TCCC）n序列在中性pH下形成i-基序结构。在PC 3细胞系中，只有当d（TCCC）n变异体足够长，在中性pH下形成显著水平的未分辨i基序结构时，才观察到缺失。实验表明，在RACK 7处的代表性d（TCCC）n元件处存在未分辨i基序，该实验表明，含有d（TCCC）9元件的区域对天然DNA中的亚硫酸氢盐攻击敏感，并且d（TCCC）9 oligo在中性pH下形成i基序结构。这反过来表明，在天然DNA中存在于该位点的i基序必须对亚硫酸氢盐介导的脱氨基敏感，即使它是封闭结构。使用质谱分析证实了模型寡脱氧核苷酸中i基序结构的亚硫酸氢盐脱氨基作用。我们的结论是，虽然G-四链体的形成可能有助于在这些网站的自发突变，删除实际上需要的i-基序形成的潜力，并保持在中性pH值未解决。
Concatemers of d(TCCC) that were first detected through their association with deletions at the RACK7 locus, are widespread throughout the human genome. Circular dichroism spectra show that d(GGGA)n sequences form G-quadruplexes when n > 3, while i-motif structures form at d(TCCC)n sequences at neutral pH when n ≥ 7 in vitro. In the PC3 cell line, deletions are observed only when the d(TCCC)n variant is long enough to form significant levels of unresolved i-motif structure at neutral pH. The presence of an unresolved i-motif at a representative d(TCCC)n element at RACK7 was suggested by experiments showing that that the region containing the d(TCCC)9 element was susceptible to bisulfite attack in native DNA and that d(TCCC)9 oligo formed an i-motif structure at neutral pH. This in turn suggested that that the i-motif present at this site in native DNA must be susceptible to bisulfite mediated deamination even though it is a closed structure. Bisulfite deamination of the i-motif structure in the model oligodeoxynucleotide was confirmed using mass spectrometry analysis. We conclude that while G-quadruplex formation may contribute to spontaneous mutation at these sites, deletions actually require the potential for i-motif to form and remain unresolved at neutral pH.
登录
查看更多内容
影响因子：
14.9
作者：
Del Mundo IMA;Zewail-Foote M;Kerwin SM;Vasquez KM
通讯作者：
Vasquez KM
影响因子：
14.9
作者：
Mergny JL;Li J;Lacroix L;Amrane S;Chaires JB
通讯作者：
Chaires JB
影响因子：
14.9
作者：
Guo K;Gokhale V;Hurley LH;Sun D
通讯作者：
Sun D
影响因子：
64.8
作者：
Raghavan, SC;Swanson, PC;Lieber, MR
通讯作者：
Lieber, MR
R环的形成是未甲基化的人类CpG岛启动子的独特特征。
影响因子：
16
作者：
Ginno PA;Lott PL;Christensen HC;Korf I;Chédin F
通讯作者：
Chédin F