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细菌中的 G-四链体结构:生物学相关性及其作为抗菌靶点的潜力。

G-Quadruplex Structures in Bacteria: Biological Relevance and Potential as an Antimicrobial Target.

机构信息

Department of Microbiology, Central University of Haryana, Mahendergarh, Haryana, India.

Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.

出版信息

J Bacteriol. 2021 Jun 8;203(13):e0057720. doi: 10.1128/JB.00577-20.

Abstract

DNA strands consisting of multiple runs of guanines can adopt a noncanonical, four-stranded DNA secondary structure known as G-quadruplex or G4 DNA. G4 DNA is thought to play an important role in transcriptional and translational regulation of genes, DNA replication, genome stability, and oncogene expression in eukaryotic genomes. In other organisms, including several bacterial pathogens and some plant species, the biological roles of G4 DNA and G4 RNA are starting to be explored. Recent investigations showed that G4 DNA and G4 RNA are generally conserved across plant species. analyses of several bacterial genomes identified putative guanine-rich, G4 DNA-forming sequences in promoter regions. The sequences were particularly abundant in certain gene classes, suggesting that these highly diverse structures can be employed to regulate the expression of genes involved in secondary metabolite synthesis and signal transduction. Furthermore, in the pathogen Mycobacterium tuberculosis, the distribution of G4 motifs and their potential role in the regulation of gene transcription advocate for the use of G4 ligands to develop novel antitubercular therapies. In this review, we discuss the various roles of G4 structures in bacterial DNA and the application of G4 DNA as inhibitors or therapeutic agents to address bacterial pathogens.

摘要

由多个鸟嘌呤组成的 DNA 链可以采用一种非典型的四链 DNA 二级结构,称为 G-四链体或 G4 DNA。人们认为 G4 DNA 在真核基因组中的基因转录和翻译调控、DNA 复制、基因组稳定性和癌基因表达中发挥着重要作用。在其他生物体中,包括一些细菌病原体和一些植物物种,G4 DNA 和 G4 RNA 的生物学作用开始被探索。最近的研究表明,G4 DNA 和 G4 RNA 在植物物种中普遍保守。对几种细菌基因组的分析鉴定了启动子区域中存在的推定富含鸟嘌呤的 G4 DNA 形成序列。这些序列在某些基因类中特别丰富,表明这些高度多样化的结构可以被用来调节涉及次生代谢物合成和信号转导的基因的表达。此外,在病原体结核分枝杆菌中,G4 基序的分布及其在基因转录调控中的潜在作用,支持使用 G4 配体开发新型抗结核疗法。在这篇综述中,我们讨论了 G4 结构在细菌 DNA 中的各种作用,以及将 G4 DNA 作为抑制剂或治疗剂来应对细菌病原体的应用。

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