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SOLUTION STRUCTURE OF A DNA QUADRUPLEX CONTAINING THE FRAGILE X SYNDROME TRIPLET REPEAT

机译:包含脆性X综合征三重链重复的DNA四倍体的溶液结构

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Both X-ray and NMR structural studies have defined the polymorphic of G-quadruplexes generated through mutual stacking of G . G . G . G tetrads by guanine rich telomeric sequences. Recently the fragile X syndrome d(C-G-G)(n) triplet nucleotide repeat has been shown to form a stable quadruplex of undefined structure in monovalent cation solution. We have undertaken a structural characterization of the d(G-C-G-G-T-3-G-C-G-G) undecanucleotide to elucidate the structural alignments associated with quadruplex formation by this oligomer which contains sequence elements associated with the fragile X syndrome triplet repeat. d(G-C-G-G-T-3-G-C-G-G) in Na+ cation solution forms a quadruplex through dimerization of two symmetry related hairpins with the lateral connecting T-3 loops positioned at opposite ends of the quadruplex. This novel NMR-molecular dynamics based solution structure contains internal G . C . G . C tetrads sandwiched between terminal G . G . G . G tetrads. Watson-Crick G . C base-pairs within individual hairpins dimerize through their major groove edges using bifurcated hydrogen bonds to form internal G(anti). C(anti). G(anti). C(anti) tetrads. Adjacent strands are anti-parallel to each other around the symmetric G-quadruplex which contains two distinct narrow and two symmetric wide grooves. By contrast, the terminal G-tetrads adopt G(syn). G(anti). G(syn). G(anti) alignments. The structure of the d(G-C-G-G-T-3-G-C-G-G) quadruplex with its multi-layer arrangement of G . G . G . G and G . C . G . C tetrads greatly expands on our current knowledge of quadruplex folding topologies. Our results establish the pairing alignments that can be potentially utilized by the fragile X syndrome triplet repeat to form quadruplex structures through dimerization of hairpin stems. The formation of novel G . C . G . C tetrads through dimerization of Watson-Crick G . C base-pairs is directly relevant to the potential pairing alignments of helical sterns in genetic recombination. (C) 1995 Academic Press Limited [References: 67]
机译:X射线和NMR结构研究都确定了通过G相互堆积而生成的G四元体的多态性。 G 。 G 。 G鸟嘌呤丰富的端粒序列四分体。最近,脆弱的X综合征d(C-G-G)(n)三联体核苷酸重复序列已显示在单价阳离子溶液中形成未定义结构的稳定四链体。我们已经对d(G-C-G-G-T-3-G-C-G-G)十一核苷酸进行了结构表征,以阐明与该四聚体形成相关的结构比对,该寡聚体包含与易碎X综合征三联体重复相关的序列元素。 Na +阳离子溶液中的d(G-C-G-G-T-3-G-C-G-G)通过两个对称相关发夹的二聚作用形成四链体,其横向连接的T-3环位于四链体的相对端。这种新颖的基于NMR分子动力学的溶液结构包含内部G。 C 。 G 。 C四极夹在端子G之间。 G 。 G 。 G四分体。沃森·克里克使用分叉的氢键,单个发夹内的C碱基对通过其主要凹槽边缘二聚,形成内部G(anti)。 C(反)。 G(anti)。 C(反)四元组相邻的绞线在包含两个不同的窄槽和两个对称宽槽的对称G-四链体周围彼此反平行。相比之下,终端G-tetrads采用G(syn)。 G(anti)。 G(syn)。 G(反)比对。 d(G-C-G-G-T-3-G-C-G-G)四层结构的多层结构。 G 。 G 。 G和G。 C 。 G 。 C quadds极大地扩展了我们当前对四重折叠拓扑的了解。我们的结果建立了配对比对结果,该序列可被脆弱的X综合征三联体重复序列利用,通过发夹茎的二聚化形成四链体结构。小说G的形成。 C 。 G 。 C通过Watson-Crick G的二聚作用形成四联体。 C碱基对与基因重组中螺旋尾的潜在配对比对直接相关。 (C)1995 Academic Press Limited [参考:67]

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