The new models of the human telomere d[AGGG(TTAGGG)3] in K+ solution

The new models of the human telomere d[AGGG(TTAGGG)3] in K+ solution
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DOI:
10.1016/j.bmc.2006.04.033
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发表时间:
2006-08-15
影响因子:
3.5
通讯作者:
Sugiyama, Hiroshi
Sugiyama, Hiroshi
中科院分区:
医学3区
文献类型:
--
作者:
Xu, Yan;Noguchi, Yuki;Sugiyama, Hiroshi

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人类端粒序列d[AGGG(TTAGGG)(3)]被发现形成不同类型的G-四链结构。核磁共振显示,在Na+溶液中,这个22个核苷酸(NT)序列呈现出反平行结构,而在K+存在下的结晶学研究显示出显著不同的平行结构。由于细胞内K+浓度大于Na+浓度,K+存在时这段22nT序列的结构引起了人们极大的兴趣。然而,在K+溶液中,22nT端粒序列的结构类型的问题仍然悬而未决。在本研究中,我们用8-溴鸟嘌呤取代了序列中的Gs,并用圆二色谱(CD)检测了产物的结构和热稳定性。结果表明,K+溶液中的22个核苷酸以混合平行/反平行和椅型G-四链体的形式存在。到目前为止,人端粒G-四链体在K+溶液中的确切结构仍存在极大争议。本研究为理解晶体和溶液研究之间的差异提供了有价值的信息。我们讨论了该结构对理解高阶端粒DNA结构和T环形成的可能意义。(C)2006年,爱思唯尔有限公司出版。
The human telomeric sequence d[AGGG (TTAGGG)(3)] has been found to form different types of G-quadruplex structures. NMR revealed that in Na+ solution this 22 nucleotide (nt) sequence exhibits an antiparallel structure, whereas crystallographic studies in the presence of K+ showed a dramatically different parallel structure. The structure of this 22 nt sequence in the presence of K+ has drawn intense interest as the intracellular K+ concentration is greater than that of Na+. However, the question of the type of structure for the 22 nt telomeric sequence in K+ solution remains open. In this study, we substituted the Gs in the sequence with 8-bromoguanine and examined the resultant structures and thermal stabilities by circular dichroism (CD) spectroscopy. The results suggest that the 22 nt in K+ solution exists as a mixture of mixed-parallel/antiparallet and chair-type G-quadruplex. To date, the exact structure of human telomeric G-quadruplex in K+ solution is extremely controversial. The present study provides valuable information for understanding the discrepancies between the crystal and solution studies. We discuss the possible implications of the structure in understanding higher-order telomeric DNA structure and T-loop formation. (c) 2006 Published by Elsevier Ltd.