Structure of the human telomere in Na+ solution: an antiparallel (2+2) G-quadruplex scaffold reveals additional diversity.

Structure of the human telomere in Na+ solution: an antiparallel (2+2) G-quadruplex scaffold reveals additional diversity.
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DOI:
10.1093/nar/gkt771
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发表时间:
2013-12
影响因子:
14.9
通讯作者:
Phan AT
Phan AT
中科院分区:
生物学2区
文献类型:
--
作者:
Lim KW;Ng VC;Martín-Pintado N;Heddi B;Phan AT

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人类端粒重复序列末端的单链DNA能够采用四链g -四重体结构,这可能是潜在的抗癌靶点。在报道的五种分子内人类端粒g -四重结构中,有四种是在K+离子存在的情况下形成的,只有一种是在Na+离子存在的情况下形成的,这常常导致人们认为这种结构多态性只发生在K+而不是Na+存在的情况下。在这里,我们提出了一个新的反平行(2+2)g -四重体的结构,它是由一个27-nt人类端粒序列在Na+溶液中的衍生物形成的,它包括一个不同于已知拓扑结构的新的核心排列。该结构补充了先前阐明的篮型人类端粒g -四重体,可作为含Na+环境中的参考结构。这些结构,以及核磁共振波谱观察到的Na+溶液中其他构象的共存,确立了人类端粒重复序列的多态性质,不受K+离子的影响。
Single-stranded DNA overhangs at the ends of human telomeric repeats are capable of adopting four-stranded G-quadruplex structures, which could serve as potential anticancer targets. Out of the five reported intramolecular human telomeric G-quadruplex structures, four were formed in the presence of K+ ions and only one in the presence of Na+ ions, leading often to a perception that this structural polymorphism occurs exclusively in the presence of K+ but not Na+. Here we present the structure of a new antiparallel (2+2) G-quadruplex formed by a derivative of a 27-nt human telomeric sequence in Na+ solution, which comprises a novel core arrangement distinct from the known topologies. This structure complements the previously elucidated basket-type human telomeric G-quadruplex to serve as reference structures in Na+-containing environment. These structures, together with the coexistence of other conformations in Na+ solution as observed by nuclear magnetic resonance spectroscopy, establish the polymorphic nature of human telomeric repeats beyond the influence of K+ ions.
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