Four-stranded DNA: cancer, gene regulation and drug development
Four-stranded DNA: cancer, gene regulation and drug development
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DOI：
10.1098/rsta.2007.0011
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发表时间：
2007-12-15
期刊：
影响因子：
5
通讯作者：
Huppert, Julian Leon
中科院分区：
文献类型：
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作者：
Huppert, Julian Leon
除了著名的双螺旋结构外，DNA还可以形成许多其他结构。特别是，特定序列的富含鸟嘌呤的DNA可以形成四链结构，称为g -四联体。本文描述了这些序列的结构形式，预测哪些序列可以以这种方式折叠的技术，以及对稳定性预测的努力。然后讨论了这些结构的生物学意义，重点讨论了它们在染色体末端端粒区的重要性，以及它们在基因启动子和mRNA中的存在，它们可能分别参与调节转录和翻译。介绍并描述了能够选择性结合这些结构的配体，以及形成g -四重结构的DNA适体；这两类化合物都已在临床试验中作为抗癌药物进行了研究。本文还概述了g -四聚体在纳米技术领域日益增长的应用。文章最后分析了该领域未来可能采取的方向，并提出了进一步重要研究的一些建议。
DNA can form many structures other than the famous double helix. In particular, guanine-rich DNA of particular sequences can form four-stranded structures, called G-quadruplexes. This article describes the structural form of these sequences, techniques for predicting which sequences can fold up in this manner and efforts towards stability prediction. It then discusses the biological significance of these structures, focusing on their importance in telomeric regions at the end of chromosomes, and their existence in gene promoters and mRNA, where they may be involved with regulating transcription and translation, respectively. Ligands that are capable of selectively binding to these structures are introduced and described, as are DNA aptamers that form G-quadruplex structures; both of these classes of compound have been investigated as anticancer agents in clinical trials. The growing use of G-quadruplexes in the nanotechnology field is also outlined. The article concludes with an analysis of future directions the field may take, with some proposals for further important studies.