Skip to Main content Skip to Navigation
Journal articles

Structure of two G-quadruplexes in equilibrium in the KRAS promoter

Abstract : KRAS is one of the most mutated oncogenes and still considered an undruggable target. An alternative strategy would consist in targeting its gene rather than the protein, specifically the formation of G-quadruplexes (G4) in its promoter. G4 are secondary structures implicated in biological processes, which can be formed among G-rich DNA (or RNA) sequences. Here we have studied the major conforma-tions of the commonly known KRAS 32R, or simply 32R, a 32 residue sequence within the KRAS Nucle-ase Hypersensitive Element (NHE) region. We have determined the structure of the two major stable con-formers that 32R can adopt and which display slow equilibrium (>ms) with each other. By using different biophysical methods, we found that the nucleotides G9, G25, G28 and G32 are particularly implicated in the exchange between these two conformations. We also showed that a triad at the 3 end further stabilizes one of the G4 conformations, while the second conformer remains more flexible and less stable.
Complete list of metadata

Cited literature [58 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02951174
Contributor : Jean-Louis Mergny Connect in order to contact the contributor
Submitted on : Monday, September 28, 2020 - 3:23:12 PM
Last modification on : Wednesday, October 14, 2020 - 4:08:39 AM
Long-term archiving on: : Tuesday, December 29, 2020 - 6:36:52 PM

File

2020 NAR_Marquevielle.pdf
Publication funded by an institution

Identifiers

Collections

`

Citation

Julien Marquevielle, Coralie Robert, Olivier Lagrabette, Mona Wahid, Anne Bourdoncle, et al.. Structure of two G-quadruplexes in equilibrium in the KRAS promoter. Nucleic Acids Research, Oxford University Press, 2020, 48, pp.9336 - 9345. ⟨10.1093/nar/gkaa387⟩. ⟨inserm-02951174⟩

Share

Metrics

Record views

65

Files downloads

71