HAIRPINS ARE FORMED BY THE SINGLE DNA STRANDS OF THE FRAGILE-X TRIPLET REPEATS - STRUCTURE AND BIOLOGICAL IMPLICATIONS
HAIRPINS ARE FORMED BY THE SINGLE DNA STRANDS OF THE FRAGILE-X TRIPLET REPEATS - STRUCTURE AND BIOLOGICAL IMPLICATIONS
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DOI：
10.1073/pnas.92.11.5199
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发表时间：
1995-05-23
影响因子：
11.1
通讯作者：
GUPTA, G
中科院分区：
文献类型：
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作者：
CHEN, XA;MARIAPPAN, SVS;GUPTA, G
脆性X DNA三联体重复序列（GGC）（n）的过度扩增和超甲基化。（GCC）（n）与单个富含G和C的单链形成发夹结构的能力相关。二维核磁共振和凝胶电泳研究表明，G-和C-丰富的单链形成发夹在生理条件下。这种发夹形成的倾向对于富含C的链比对于富含G的链更明显。这一观察结果表明，富含C的链更有可能形成发夹或“滑动”结构，并在复制过程中显示不对称的链扩张。NMR数据还显示，由富含C的链形成的发夹以这样的方式折叠，即茎的CpG步骤处的胞嘧啶是C。C配对。C的存在。CPG位点的C错配产生局部灵活性，从而提供向甲基转移酶过渡的类似物。换句话说，富C链的发夹比沃森-克里克双链体或富G链作为人甲基转移酶的更好的底物。因此，发夹形成可以解释在疾病发作期间FMR 1基因失活期间发生的脆性X重复序列中CpG岛的特异性甲基化。
Inordinate expansion and hypermethylation of the fragile X DNA triplet repeat, (GGC)(n) .(GCC)(n), are correlated with the ability of the individual G- and C-rich single strands to form hairpin structures. Two-dimensional NMR and gel electrophoresis studies show that both the G- and C-rich single strands form hairpins under physiological conditions. This propensity of hairpin formation is more pronounced for the C-rich strand than for the G-rich strand. This observation suggests that the C-rich strand is more likely to form hairpin or ''slippage'' structure and show asymmetric strand expansion during replication. NMR data also show that the hairpins formed by the C-rich strands fold in such a way that the cytosine at the CpG step of the stem is C . C paired. The presence of a C . C mismatch at the CPG site generates local flexibility, thereby providing analogs of the transition to the methyltransferase. In other words, the hairpins of the C-rich strand act as better substrates for the human methyltransferase than the Watson-Crick duplex or the G-rich strand. Therefore, hairpin formation could account for the specific methylation of the CpG island in the fragile X repeat that occurs during inactivation of the FMR1 gene during the onset of the disease.