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

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dc.contributor.authorMeier, Markus
dc.contributor.authorMoya-Torres, Aniel
dc.contributor.authorKrahn, Natalie J.
dc.contributor.authorMcDougall, Matthew D.
dc.contributor.authorOrriss, George L.
dc.contributor.authorMcRae, Ewan K. S.
dc.contributor.authorBooy, Evan P.
dc.contributor.authorMcEleney, Kevin
dc.contributor.authorPatel, Trushar R.
dc.contributor.authorMcKenna, Sean A.
dc.contributor.authorStetefeld, Jorg
dc.date.accessioned2024-06-20T19:59:26Z
dc.date.available2024-06-20T19:59:26Z
dc.date.issued2018
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
dc.description.abstractThe 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.
dc.identifier.citationMeier, M., Moya-Torres, A., Krahn, N. J., McDougall, M. D., Orriss, G. L., McRae, E. K. S., Booy, E. P., McEleney, K., Patel, T. R., McKenna, S. A., & Stetefeld, J. (2018). Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge. Nucleic Acids Research, 46(10), 5319-5331. https://doi.org/10.1093/nar/gky307
dc.identifier.urihttps://hdl.handle.net/10133/6792
dc.language.isoen
dc.publisherOxford University Press
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Manitoba
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.institutionUniversity of Alberta
dc.publisher.institutionUniversity of Calgary
dc.subjectG-quadruplexes
dc.subjectRNA
dc.subjectDNA
dc.subjectCytosine bulge
dc.subject.lcshQuadruplex nucleic acids
dc.titleStructure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge
dc.typeArticle
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