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Nucleic Acids Research
Article . 2018 . Peer-reviewed
License: CC BY
Data sources: Crossref
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Nucleic Acids Research
Article
License: CC BY
Data sources: UnpayWall
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PubMed Central
Other literature type . 2018
License: CC BY
Data sources: PubMed Central
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Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge

Authors: Markus Meier; Aniel Moya-Torres; Natalie J Krahn; Matthew D McDougall; George L Orriss; Ewan K S McRae; Evan P Booy; +4 Authors

Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge

Abstract

The identification of four-stranded G-quadruplexes (G4s) has highlighted the fact that DNA has additional spatial organisations at its disposal other than double-stranded helices. Recently, it became clear that the formation of G4s is not limited to the traditional G3+NL1G3+NL2G3+NL3G3+ sequence motif. Instead, the G3 triplets can be interrupted by deoxythymidylate (DNA) or uridylate (RNA) where the base forms a bulge that loops out from the G-quadruplex core. Here, we report the first high-resolution X-ray structure of a unique unimolecular DNA G4 with a cytosine bulge. The G4 forms a dimer that is stacked via its 5'-tetrads. Analytical ultracentrifugation, static light scattering and small angle X-ray scattering confirmed that the G4 adapts a predominantly dimeric structure in solution. We provide a comprehensive comparison of previously published G4 structures containing bulges and report a special γ torsion angle range preferentially populated by the G4 core guanylates adjacent to bulges. Since the penalty for introducing bulges appears to be negligible, it should be possible to functionalize G4s by introducing artificial or modified nucleotides at such positions. The presence of the bulge alters the surface of the DNA, providing an opportunity to develop drugs that can specifically target individual G4s.

Country
Canada
Keywords

Models, Molecular, DNA, 612, Crystallography, X-Ray, G-quadruplexes, Dynamic Light Scattering, Cytosine bulge, G-Quadruplexes, Molecular Weight, Cytosine, Quadruplex nucleic acids, X-Ray Diffraction, Structural Biology, Scattering, Small Angle, Chromatography, Gel, RNA, Nucleic Acid Conformation, Telomerase

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
49
Top 10%
Top 10%
Top 1%
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