NMR solution structure of an asymmetric intermolecular leaped V-shape G-quadruplex: selective recognition of the d(G2NG3NG4) sequence motif by a short linear G-rich DNA probe

Abstract Aside from classical loops among G-quadruplexes, the unique leaped V-shape scaffold spans over three G-tetrads, without any intervening residues. This scaffold enables a sharp reversal of two adjacent strand directions and simultaneously participates in forming the G-tetrad core. These feat...

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Bibliographic Details
Published in:Nucleic acids research 2019-02, Vol.47 (3), p.1544-1556
Main Authors: Wan, Chanjuan, Fu, Wenqiang, Jing, Haitao, Zhang, Na
Format: Article
Language:English
Subjects:
Base Sequence - genetics
DNA - chemistry
DNA - genetics
DNA Probes - chemistry
DNA Probes - genetics
G-Quadruplexes
Kinetics
Magnetic Resonance Spectroscopy
Nucleic Acid Conformation
Solutions
Structural Biology
Telomere - chemistry
Telomere - genetics
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Summary:Abstract Aside from classical loops among G-quadruplexes, the unique leaped V-shape scaffold spans over three G-tetrads, without any intervening residues. This scaffold enables a sharp reversal of two adjacent strand directions and simultaneously participates in forming the G-tetrad core. These features make this scaffold itself distinctive and thus an essentially more accessible target. As an alternative to the conventional antisense method using a complementary chain, forming an intermolecular G-quadruplex from two different oligomers, in which the longer one as the target is captured by a short G-rich fragment, could be helpful for recognizing G-rich sequences and structural motifs. However, such an intermolecular leaped V-shape G-quadruplex consisting of DNA oligomers of quite different lengths has not been evaluated. Here, we present the first nuclear magnetic resonance (NMR) study of an asymmetric intermolecular leaped V-shape G-quadruplex assembled between an Oxytricha nova telomeric sequence d(G2T4G4T4G4) and a single G-tract fragment d(TG4A). Furthermore, we explored the selectivity of this short fragment as a potential probe, examined the kinetic discrimination for probing a specific mutant, and proposed the key sequence motif d(G2NG3NG4) essential for building the leaped V-shape G-quadruplexes.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gky1167