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], htel21T₁₈. 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 htel21T₁₈ 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 A6·T18 base pair. The loops are edgewise; glycosidic conformation of guanines is syn·anti·syn·anti 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.

中文翻译：

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由人端粒变体DNA在K +溶液中形成的椅子型G四联体结构。

已知人类端粒DNA序列的鸟嘌呤折叠成八种不同的四链结构，其结构因排列在其核心中G-tetrads堆栈中的鸟嘌呤核苷酸的构象以及不同类型和顺序的连接环（称为G-四重体。在这里，我们介绍由人端粒变体d [（GGGTTA）2GGGTTTGGG]，htel21 T ₁₈在K ⁺溶液中形成的新型G-四链体结构。此变体DNA位于人类染色体8、11、17和19的亚端粒区域以及DNA酶超敏区和5号染色体的亚着丝粒区域。有趣的是，使htel21 T _18的单个A18T取代与人类端粒序列不同的是，形成了三层椅子型G四联体，这是人类端粒重复序列中以前未知的折叠，其中两个环通过反向的Watson-Crick A6·T18碱基对相互作用。循环是沿边的；鸟嘌呤的糖苷构象在每个四联体周围是syn · anti · syn · anti，并且核心的每条链具有两条反平行的相邻链。我们的研究结果扩展了已知的G-四链体折叠拓扑结构，并可能为基于结构的抗癌药物设计提供潜在的目标。