A Minimal Sequence for Left-Handed G-Quadruplex Formation
A Minimal Sequence for Left-Handed G-Quadruplex Formation
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DOI：
10.1002/anie.201812628
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发表时间：
2019-02-18
影响因子：
16.6
通讯作者：
Anh Tuan Phan
中科院分区：
文献类型：
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作者：
Bakalar, Blaz;Heddi, Brahim;Anh Tuan Phan
最近，我们观察到了第一个由天然DNA形成的左手G-四链结构的例子，命名为Z-G4。我们分析了Z-G4的结构，并检查了其原始的28-NT序列，以确定表达独特的左手扭转的基序。利用圆二色谱、核磁共振谱和X射线结晶学，我们揭示了形成左手DNA G-四联体的最小序列基序(GTGGTGGGGGGGTG)，它在人类基因组中高度丰富。对胸腺嘧啶环突变的系统分析揭示了中等的序列耐受性，这将进一步拓宽倾向于左手G-四链形成的序列的空间。
Recently, we observed the first example of a left-handed G-quadruplex structure formed by natural DNA, named Z-G4. We analysed the Z-G4 structure and inspected its primary 28-nt sequence in order to identify motifs that convey the unique left-handed twist. Using circular dichroism spectroscopy, NMR spectroscopy, and X-ray crystallography, we revealed a minimal sequence motif of 12 nt (GTGGTGGTGGTG) for formation of the left-handed DNA G-quadruplex, which is found to be highly abundant in the human genome. A systematic analysis of thymine loop mutations revealed a moderate sequence tolerance, which would further broaden the space of sequences prone to left-handed G-quadruplex formation.