Human telomeric DNA: G-quadruplex, i-motif and watson-crick double helix

Human telomeric DNA: G-quadruplex, i-motif and watson-crick double helix
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DOI:
10.1093/nar/gkf597
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发表时间:
2002-11-01
影响因子:
14.9
通讯作者:
Mergny, JL
Mergny, JL
中科院分区:
生物学2区
文献类型:
--
作者:
Phan, AT;Mergny, JL

文献摘要

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人端粒DNA由(TTAGGG/CCCTAA)(N)重复序列组成,可能形成典型的Watson-Crick双螺旋结构。每个单独的链也容易形成四链:富G链可能采用包含G-四联体的G-四链构象,而富C链可能折叠成基于插入的C.C+碱基对的I-基序。使用端粒寡核苷酸d[AGGG(TTAGGG)(3)]和d[(CCCTAA)(3)CCCT]的等摩尔混合物,我们确定了在各种实验条件下哪些结构存在,哪些将是优势物种。在接近生理的pH、温度和盐浓度条件下,端粒DNA主要以双螺旋形式存在。然而,在较低的pH值或较高的温度下,G-四链体和/或I-基序与双链有效竞争。我们还给出了双链缔合和G-四链/I-基序展开的动力学和热力学数据。
Human telomeric DNA composed of (TTAGGG/CCCTAA)(n) repeats may form a classical Watson-Crick double helix. Each individual strand is also prone to quadruplex formation: the G-rich strand may adopt a G-quadruplex conformation involving G-quartets whereas the C-rich strand may fold into an i-motif based on intercalated C.C+ base pairs. Using an equimolar mixture of the telomeric oligonucleotides d[AGGG(TTAGGG)(3)] and d[(CCCTAA)(3)CCCT], we defined which structures existed and which would be the predominant species under a variety of experimental conditions. Under near-physiological conditions of pH, temperature and salt concentration, telomeric DNA was predominantly in a double-helix form. However, at lower pH values or higher temperatures, the G-quadruplex and/or the i-motif efficiently competed with the duplex. We also present kinetic and thermodynamic data for duplex association and for G-quadruplex/i-motif unfolding.