Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge
Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge
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.
- University of Alberta Canada
- University of Calgary Canada
- University of Lethbridge Canada
- University of Manitoba Canada
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
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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