Zhang Na, Phan Anh Tuân, Patel Dinshaw J
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J Am Chem Soc. 2005 Dec 14;127(49):17277-85. doi: 10.1021/ja0543090.
We present an NMR study on the structure of a DNA fragment of the human telomere containing three guanine-tracts, d(GGGTTAGGGTTAGGGT). This sequence forms in Na(+) solution a unique asymmetric dimeric quadruplex, in which the G-tetrad core involves all three G-tracts of one strand and only the last 3'-end G-tract of the other strand. We show that a three-repeat human telomeric sequence can also associate with a single-repeat human telomeric sequence into a structure with the same topology that we name (3 + 1) quadruplex assembly. In this G-quadruplex assembly, there are one syn.syn.syn.anti and two anti.anti.anti.syn G-tetrads, two edgewise loops, three G-tracts oriented in one direction and the fourth oriented in the opposite direction. We discuss the possible implications of the new folding topology for understanding the structure of telomeric DNA, including t-loop formation, and for targeting G-quadruplexes in the telomeres.
我们展示了一项关于人类端粒DNA片段d(GGGTTAGGGTTAGGGT)结构的核磁共振研究,该片段包含三个鸟嘌呤链。此序列在Na(+)溶液中形成一种独特的不对称二聚体四链体,其中G-四联体核心涉及一条链的所有三个鸟嘌呤链以及另一条链仅最后的3'-末端鸟嘌呤链。我们表明,一个三重复的人类端粒序列也可与一个单重复的人类端粒序列缔合形成具有相同拓扑结构的结构,我们将其命名为(3 + 1)四链体组装体。在这个G-四链体组装体中,有一个顺式.顺式.顺式.反式和两个反式.反式.反式.顺式G-四联体,两个边缘环,三个朝一个方向排列的鸟嘌呤链以及第四个朝相反方向排列的鸟嘌呤链。我们讨论了这种新折叠拓扑结构对于理解端粒DNA结构(包括t环形成)以及靶向端粒中的G-四链体的可能意义。