Quadruplexes are noncanonical DNA structures that arise in guanine rich loci and have important biological functions. Classically, quadruplexes contain four stacked intramolecular G-tetrads. Surprisingly, although some algorithms allow searching for longer than 4G tracts for quadruplex formation, these have not yet been systematically studied. Therefore, we analyzed the human genome for sequences that are predicted to adopt stacked intramolecular G-tetrads with greater than four stacks. The data provide evidence for numerous G-quadruplexes that contain five or six stacked intramolecular G-tetrads. These sequences are predominantly found in known gene regulatory regions. Electrophoretic mobility assays and circular dichroism spectroscopy indicate that these sequences form quadruplex structures in vitro under physiological conditions. The localization and in vitro stability of these G-quadruplexes indicate their potentially important roles in gene regulation and their potential for therapeutic applications.

四重体是在鸟嘌呤丰富的基因座中出现的非规范DNA结构，具有重要的生物学功能。传统上，四链体包含四个堆叠的分子内G-四联体。出人意料的是，尽管一些算法允许搜索比4G更长的序列来形成四链体，但是尚未对它们进行系统地研究。因此，我们分析了人类基因组中的序列，这些序列预计将采用具有四个以上堆叠结构的堆叠分子内G-四联体。数据提供了许多G-四链体的证据，这些G-四链体包含五个或六个堆叠的分子内G-四联体。这些序列主要存在于已知的基因调节区。电泳迁移率测定和圆二色性光谱表明，这些序列在体外形成四链体结构在生理条件下。这些G-四链体的定位和体外稳定性表明它们在基因调控中的潜在重要作用及其在治疗中的潜力。