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DNA和RNA G-四链体的结构、性质及生物学相关性:发现50年后的综述

Structure, Properties, and Biological Relevance of the DNA and RNA G-Quadruplexes: Overview 50 Years after Their Discovery.

作者信息

Dolinnaya N G, Ogloblina A M, Yakubovskaya M G

机构信息

Lomonosov Moscow State University, Department of Chemistry, Moscow, 119991, Russia.

出版信息

Biochemistry (Mosc). 2016 Dec;81(13):1602-1649. doi: 10.1134/S0006297916130034.

DOI:10.1134/S0006297916130034
PMID:28260487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7087716/
Abstract

G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding-unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA-RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4-specific small-molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G-quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweezers, original chemical approaches, G4 detection in situ, in-cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G-quadruplexes.

摘要

G-四链体(G4s)是目前研究最为活跃的非经典核酸结构,已知其在正常细胞和病理细胞的关键生物学过程调控中发挥重要作用。在本综述中,我们总结了近年来发表的研究成果,这些成果显著改变了我们对四链体各方面的科学认识。本文讨论了关于DNA四链体多态性、影响G4折叠-解折叠热力学和动力学的因素、多四链体系统的结构组织以及RNA G4和DNA-RNA杂交G4构象特征的现代概念。我们报道了真核生物、细菌和病毒基因组中G4序列基序的定位数据,表征了G4特异性小分子配体和蛋白质,以及它们与四链体相互作用的机制。还讨论了端粒DNA和癌基因启动子中G4结构和稳定性的新信息,并提供了细胞中存在G-四链体的证据。重点介绍了有助于G-四链体结构和功能研究取得突破的新型实验技术(单分子操作、光学和磁性镊子、原创化学方法、原位G4检测、细胞内核磁共振光谱)。

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Biophys J. 2016 May 24;110(10):2169-75. doi: 10.1016/j.bpj.2016.04.031.
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G-register exchange dynamics in guanine quadruplexes.鸟嘌呤四链体中的鸟嘌呤寄存器交换动力学
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Mutually Exclusive Formation of G-Quadruplex and i-Motif Is a General Phenomenon Governed by Steric Hindrance in Duplex DNA.G-四链体和i-基序的互斥形成是双链DNA中空间位阻控制的普遍现象。
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Molecular dynamics simulations reveal the balance of forces governing the formation of a guanine tetrad-a common structural unit of G-quadruplex DNA.分子动力学模拟揭示了控制鸟嘌呤四联体(G-四链体DNA的常见结构单元)形成的力的平衡。
Nucleic Acids Res. 2016 Apr 20;44(7):3020-30. doi: 10.1093/nar/gkw160. Epub 2016 Mar 14.
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A novel transition pathway of ligand-induced topological conversion from hybrid forms to parallel forms of human telomeric G-quadruplexes.一种新型的配体诱导的人类端粒G-四链体从杂交形式到平行形式的拓扑转换途径。
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RNA G-Quadruplex Invasion and Translation Inhibition by Antisense γ-Peptide Nucleic Acid Oligomers.反义γ-肽核酸寡聚物对RNA G-四链体的侵入及翻译抑制作用
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Can We Execute Reliable MM-PBSA Free Energy Computations of Relative Stabilities of Different Guanine Quadruplex Folds?我们能否对不同鸟嘌呤四链体折叠的相对稳定性进行可靠的MM-PBSA自由能计算?
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