左手性 G-四链体形成的最小序列。

A Minimal Sequence for Left-Handed G-Quadruplex Formation.

机构信息

School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.

School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore.

出版信息

Angew Chem Int Ed Engl. 2019 Feb 18;58(8):2331-2335. doi: 10.1002/anie.201812628. Epub 2019 Jan 21.

DOI:10.1002/anie.201812628

PMID:30481397

Abstract

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.

摘要

最近，我们观察到了第一个由天然 DNA 形成的左手 G-四链体结构，命名为 Z-G4。我们分析了 Z-G4 结构，并检查了其主要的 28 个核苷酸序列，以识别传递独特左手扭曲的模体。使用圆二色性光谱、NMR 光谱和 X 射线晶体学，我们揭示了一个最小的 12 个核苷酸（GTGGTGGTGGTG）序列基序，用于形成左手 DNA G-四链体，该基序在人类基因组中高度丰富。对胸腺嘧啶环突变的系统分析显示出中等的序列容忍度，这将进一步扩大易于形成左手 G-四链体的序列空间。