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

J 2020

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

MARQUEVIELLE, Julien, Coralie ROBERT, Olivier LAGRABETTE, Mona WAHID, Anne BOURDONCLE et. al.

Basic information

Original name

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

Authors

MARQUEVIELLE, Julien, Coralie ROBERT, Olivier LAGRABETTE, Mona WAHID, Anne BOURDONCLE, Luigi E XODO, Jean-Louis MERGNY and Gilmar F SALGADO

Edition

Nucleic acids research, Oxford, Oxford University Press, 2020, 0305-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 16.971

DOI

http://dx.doi.org/10.1093/nar/gkaa387

UT WoS

000574332700042

Keywords in English

THROUGH-BOND CORRELATION; PANCREATIC-CANCER CELLS; CIRCULAR-DICHROISM; RAS; DNA; POLYMORPHISM; BIND; CRYSTALLOGRAPHY; RESONANCES; MUTATIONS

Abstract

V originále

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 conformations of the commonly known KRAS 32R, or simply 32R, a 32 residue sequence within the KRAS Nuclease Hypersensitive Element (NHE) region. We have determined the structure of the two major stable conformers 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.

Links

90127, large research infrastructures

Name: CIISB II

Citovat

MARQUEVIELLE, Julien, Coralie ROBERT, Olivier LAGRABETTE, Mona WAHID, Anne BOURDONCLE, Luigi E XODO, Jean-Louis MERGNY and Gilmar F SALGADO. Structure of two G-quadruplexes in equilibrium in the KRAS promoter. Nucleic acids research. Oxford: Oxford University Press, 2020, vol. 48, No 16, p. 9336-9345. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkaa387.

@article{2409808,
   author = {Marquevielle, Julien and Robert, Coralie and Lagrabette, Olivier and Wahid, Mona and Bourdoncle, Anne and Xodo, Luigi E and Mergny, JeanandLouis and Salgado, Gilmar F},
   article_location = {Oxford},
   article_number = {16},
   doi = {http://dx.doi.org/10.1093/nar/gkaa387},
   keywords = {THROUGH-BOND CORRELATION; PANCREATIC-CANCER CELLS; CIRCULAR-DICHROISM; RAS; DNA; POLYMORPHISM; BIND; CRYSTALLOGRAPHY; RESONANCES; MUTATIONS},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic acids research},
   title = {Structure of two G-quadruplexes in equilibrium in the KRAS promoter},
   url = {https://academic.oup.com/nar/article/48/16/9336/5841130?login=true},
   volume = {48},
   year = {2020}
}

TY  - JOUR
ID  - 2409808
AU  - Marquevielle, Julien - Robert, Coralie - Lagrabette, Olivier - Wahid, Mona - Bourdoncle, Anne - Xodo, Luigi E - Mergny, Jean-Louis - Salgado, Gilmar F
PY  - 2020
TI  - Structure of two G-quadruplexes in equilibrium in the KRAS promoter
JF  - Nucleic acids research
VL  - 48
IS  - 16
SP  - 9336-9345
EP  - 9336-9345
PB  - Oxford University Press
SN  - 03051048
KW  - THROUGH-BOND CORRELATION
KW  - PANCREATIC-CANCER CELLS
KW  - CIRCULAR-DICHROISM
KW  - RAS
KW  - DNA
KW  - POLYMORPHISM
KW  - BIND
KW  - CRYSTALLOGRAPHY
KW  - RESONANCES
KW  - MUTATIONS
UR  - https://academic.oup.com/nar/article/48/16/9336/5841130?login=true
N2  - 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 conformations of the commonly known KRAS 32R, or simply 32R, a 32 residue sequence within the KRAS Nuclease Hypersensitive Element (NHE) region. We have determined the structure of the two major stable conformers 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.
ER  -

MARQUEVIELLE, Julien, Coralie ROBERT, Olivier LAGRABETTE, Mona WAHID, Anne BOURDONCLE, Luigi E XODO, Jean-Louis MERGNY and Gilmar F SALGADO. Structure of two G-quadruplexes in equilibrium in the KRAS promoter. \textit{Nucleic acids research}. Oxford: Oxford University Press, 2020, vol.~48, No~16, p.~9336-9345. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkaa387.

Detailed Information on Publication Record