A chair-type G-quadruplex structure formed by a human telomeric variant DNA in K+ solution
A chair-type G-quadruplex structure formed by a human telomeric variant DNA in K+ solution
复制标题
由人端粒变异DNA在K溶液中形成的椅型G-四链体结构。
DOI：
10.1039/c8sc03813a
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发表时间：
2019-01-07
期刊：
影响因子：
8.4
通讯作者：
Zhu, Guang
中科院分区：
文献类型：
--
作者：
Liu, Changdong;Zhou, Bo;Zhu, Guang
已知的人类端粒DNA序列的鸟嘌呤序列折叠成8个不同的四链结构，这些结构因其核心G-四分体堆叠中鸟嘌呤核苷酸的构象以及连接环的不同种类和顺序而异，称为G-四链。在这里，我们提出了一种由人端粒突变体d[(GGGTTA)2GGGTTTGGG]，htel21T(18)在K+溶液中形成的新的G-四链结构。这种变异DNA位于人类8、11、17和19号染色体的亚端粒区域以及5号染色体的DNA酶超敏感区和亚着丝粒区域。有趣的是，单个A18T替换使htel21T(18)不同于人类端粒序列，导致形成一个三层椅型G-四链，这是以前在人类端粒重复序列中未知的折叠，有两个环通过反向的Watson-Crick A6T18碱基对相互作用。环呈边状；鸟嘌呤类化合物的糖苷构象是围绕每个四分体的联结构象，核心的每条链都有两条反平行的相邻链。我们的结果扩展了已知的G-四链折叠拓扑结构，并可能为基于结构的抗癌药物设计提供潜在的靶点。
Guanine tracts of human telomeric DNA sequences are known to fold into eight different four-stranded structures that vary by the conformation of guanine nucleotides arranged in the stack of G-tetrads in their core and by different kinds and orders of connecting loops, called G-quadruplexes. Here, we present a novel G-quadruplex structure formed in K+ solution by a human telomeric variant d[(GGGTTA)2GGGTTTGGG], htel21T(18). This variant DNA is located in the subtelomeric regions of human chromosomes 8, 11, 17, and 19 as well as in the DNase hypersensitive region and in the subcentromeric region of chromosome 5. Interestingly, single A18T substitution that makes htel21T(18) different from the human telomeric sequence results in the formation of a three-layer chair-type G-quadruplex, a fold previously unknown among human telomeric repeats, with two loops interacting through the reverse Watson-Crick A6T18 base pair. The loops are edgewise; glycosidic conformation of guanines is synantisynanti around each tetrad, and each strand of the core has two antiparallel adjacent strands. Our results expand the repertoire of known G-quadruplex folding topologies and may provide a potential target for structure-based anticancer drug design.