Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge
Autor: | Ewan K.S. McRae, Natalie Krahn, Kevin McEleney, Aniel Moya-Torres, George L. Orriss, Jörg Stetefeld, Trushar R. Patel, Matthew McDougall, Markus Meier, Evan P. Booy, Sean A. McKenna |
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Rok vydání: | 2018 |
Předmět: |
Models
Molecular 0301 basic medicine Dimer Biology Crystallography X-Ray 010402 general chemistry G-quadruplex 01 natural sciences Cytosine 03 medical and health sciences chemistry.chemical_compound X-Ray Diffraction Structural Biology Bulge Scattering Small Angle Genetics A-DNA Telomerase RNA Dynamic Light Scattering 0104 chemical sciences G-Quadruplexes Molecular Weight Crystallography 030104 developmental biology chemistry Chromatography Gel Nucleic Acid Conformation Sequence motif DNA |
Zdroj: | Nucleic Acids Research |
ISSN: | 1362-4962 0305-1048 |
Popis: | 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. |
Databáze: | OpenAIRE |
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