Structure and K+ ion-dependent stability of a parallel-stranded DNA quadruplex containing a core A-tetrad.
The c-MYC oncogene, containing the DNA 5'-GGAGG repeat sequence, is emerging as an attractive target for anti-cancer therapeutics with evidence to suggest that DNA quadruplex formation is involved in regulating gene transcription. We describe NMR studies and molecular dynamics (MD) simulations on intermolecular quadruplex structures containing the purine-rich GGAGG motif which we show readily assembles to form stable parallel-stranded quadruplexes containing A- and G-tetrads with evidence for weak sequence-specific K(+) ion binding at the 5'-GA step.
School of Chemistry, Centre for Biomolecular Sciences, University Park, Nottingham, UK NG7 2RD.
Mark S
MS
Searle
Huw E L
HE
Williams
Cathal T
CT
Gallagher
Richard J
RJ
Grant
Malcolm F G
MF
Stevens
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D002412:Cations; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011188:Potassium / Q000737:chemistry*; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry; D011687:Purines / Q000737:chemistry; D012091:Repetitive Sequences, Nucleic Acid
D000970:Antineoplastic Agents; D002412:Cations; D016271:Proto-Oncogene Proteins c-myc; D011687:Purines; D004247:DNA; D011188:Potassium; C030985:purine