Involvement of G-triplex and G-hairpin in the multi-pathway folding of human telomeric G-quadruplex.

Involvement of G-triplex and G-hairpin in the multi-pathway folding of human telomeric G-quadruplex.
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G-三链体和 G-发夹参与人端粒 G-四链体的多途径折叠

DOI:
10.1093/nar/gkx766
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发表时间:
2017-11-02
影响因子:
14.9
通讯作者:
Xi XG
Xi XG
中科院分区:
生物学2区
文献类型:
--
作者:
Hou XM;Fu YB;Wu WQ;Wang L;Teng FY;Xie P;Wang PY;Xi XG

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摘要G-四链体(G4)是广泛分布于人类基因组中的富含G的DNA序列。虽然G-triplex和G-hairpin被认为是G4折叠的中间体,但它们的形成仍需要进一步的实验研究。在这里,我们采用单分子FRET来表征从人类端粒序列G4的折叠动力学。首先,我们在G4折叠过程中观察到四种状态,最初被分配为反平行G4,G-triplex,G-hairpin和未折叠的ssDNA。然后,我们构建了推定的链内G-三链体,G-发夹结构,并证实它们在NaCl和KCl中的存在。进一步的研究表明,这些结构正在经历不同状态之间的动态转变,并且与G4不同,对阳离子的依赖性相对较弱。基于这些结果和分子动力学模拟,我们提出了一个多途径折叠机制的端粒G4。本文的工作可能对我们目前对G4中间态的存在性和稳定性的理解有新的启示。
Abstract G-quadruplex (G4) can be formed by G-rich DNA sequences that are widely distributed throughout the human genome. Although G-triplex and G-hairpin have been proposed as G4 folding intermediates, their formation still requires further investigation by experiments. Here, we employed single-molecule FRET to characterize the folding dynamics of G4 from human telomeric sequence. First, we observed four states during G4 folding initially assigned to be anti-parallel G4, G-triplex, G-hairpin and unfolded ssDNA. Then we constructed putative intra-strand G-triplex, G-hairpin structures and confirmed their existences in both NaCl and KCl. Further studies revealed those structures are going through dynamic transitions between different states and show relatively weak dependence on cations, unlike G4. Based on those results and molecular dynamics simulations, we proposed a multi-pathway folding mechanism for human telomeric G4. The present work may shed new light on our current understanding about the existence and stability of G4 intermediate states.
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发表时间: 2014-12-01
影响因子: 14.9
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