Burge Sarah, Parkinson Gary N, Hazel Pascale, Todd Alan K, Neidle Stephen
Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Nucleic Acids Res. 2006;34(19):5402-15. doi: 10.1093/nar/gkl655. Epub 2006 Sep 29.
G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential quadruplex sequences have been identified in G-rich eukaryotic telomeres, and more recently in non-telomeric genomic DNA, e.g. in nuclease-hypersensitive promoter regions. The natural role and biological validation of these structures is starting to be explored, and there is particular interest in them as targets for therapeutic intervention. This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence. Emphasis is placed on information from the high-resolution methods of X-ray crystallography and NMR, and their scope and current limitations are discussed. Such information, together with biological insights, will be important for the discovery of drugs targeting quadruplexes from particular genes.
G-四链体是由富含鸟嘌呤的序列形成的高阶DNA和RNA结构，这些序列围绕着由氢键连接的鸟嘌呤碱基组成的四联体构建而成。在富含鸟嘌呤的真核生物端粒中已鉴定出潜在的四链体序列，最近在非端粒基因组DNA中也有发现，例如在核酸酶超敏启动子区域。这些结构的天然作用和生物学验证正开始被探索，并且它们作为治疗干预的靶点受到了特别关注。本综述聚焦于由端粒和非端粒DNA序列形成的四链体的折叠和结构特征，研究拓扑学的基本方面以及与序列的新关系。重点是来自X射线晶体学和核磁共振等高分辨率方法的信息，并讨论了它们的范围和当前局限性。这些信息以及生物学见解对于发现针对特定基因四链体的药物将非常重要。
