G-quadruplexes in fibrotic scars may open new therapeutic avenues for wound healing.

G-quadruplexes in fibrotic scars may open new therapeutic avenues for wound healing.
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DOI:
10.1002/1873-3468.13711
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发表时间:
2020-01
期刊:
影响因子:
3.5
通讯作者:
Yatsunyk LA
Yatsunyk LA
中科院分区:
生物学3区
文献类型:
--
作者:
Johnson FB;Yatsunyk LA

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除了沃森-克里克双链螺旋之外,DNA 还可以存在于多种非规范结构中。自 20 世纪 60 年代以来,人们就知道鸟嘌呤含量高的 DNA 序列可以折叠成螺旋结构,由堆叠的 G-四分体组成,称为 G-四联体 (G4)[1]。每个 G-四分体都是通过 Hoogsteen 氢键连接的四个鸟嘌呤的稳定排列。生物 G4 通常被认为是由两到四个 G 四分体堆叠形成的单分子结构,通过单价阳离子(通常是 K+)进一步稳定,单价阳离子结合在每对 G 四分体之间的中心空腔中。虽然 G4 的体外形成已得到明确证明,但它们在生物系统中的存在和功能作用仍是一个深入研究的问题 [2]。总体而言,有新的证据表明 G4 在基因表达调控以及 DNA 复制和修复中发挥作用。 G4 生物形成的一些证据来自使用抗 G4 抗体的研究,其中最著名的是 BG4 单链抗体片段,它在体外以明显高选择性结合 G4 DNA 和 RNA 结构 [3]。 BG4 优先免疫沉淀具有高四联体形成潜力 (QFP) 的染色质区域,并且通过删除解旋 G4 DNA 的 DNA 解旋酶来增强复制染色质的 BG4 染色,从而提供了 BG4 可以在体内识别 G4 的一些证据 [4, 5]。然而,关于 BG4 可能在多大程度上与生物样品中的交叉反应靶标结合,甚至诱导和稳定自然不存在的 G4 折叠,目前还没有多少信息。因此,固定细胞的 BG4 染色本身应被视为体内 G4 的临时证据。
DNA can exist in a variety of noncanonical structures in addition to Watson–Crick doublestranded helix. It has been known since the 1960s that DNA sequences with high guanine content can fold into a helical structure, composed of stacked G-tetrads, termed G-quadruplex (G4)[1]. Each G-tetrad is a stable arrangement of four guanines connected via Hoogsteen hydrogen bonding. Biological G4s are typically thought to be monomolecular structures formed by stacks of two to four G-tetrads further stabilized by a monovalent cation (often K+), which binds in a central cavity between each pair of G-tetrads.While in vitro formation of G4s has been clearly demonstrated, their existence and functional roles in biological systems are a matter of intense investigation [2]. Overall, there is emerging evidence for G4 roles in the regulation of gene expression and in DNA replication and repair. Some evidence for biological G4 formation has come from studies employing anti-G4 antibodies, most prominently the BG4 single-chain antibody fragment, which binds G4 DNA and RNA structures with apparently high selectivity in vitro [3]. BG4 preferentially immunoprecipitates chromatin regions with high quadruplex-forming potential (QFP), and BG4 staining of replicating chromatin is enhanced by the deletion of DNA helicases that unwind G4 DNA, thus providing some evidence that BG4 can recognize G4s in vivo [4, 5]. However, there is little information about the extent to which BG4 might bind to cross-reactive targets in biological samples, or even induce and stabilize G4 folds that do not exist naturally. Thus, BG4 staining of fixed cells should, by itself, be considered provisional evidence of G4s in vivo.
G-四链体折叠和稳定性中的金属阳离子。
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