title: Putative DNA quadruplex formation within the human c-kit oncogene.
abstract: The DNA sequence, d(AGGGAGGGCGCTGGGAGGAGGG), occurs within the promoter region of the c-kit oncogene. We show here, using a combination of NMR, circular dichroism, and melting temperature measurements, that this sequence forms a four-stranded quadruplex structure under physiological conditions. Variations in the sequences that intervene between the guanine tracts have been examined, and surprisingly, none of these modified sequences forms a quadruplex arrangement under these conditions. This suggests that the occurrence of quadruplex-forming sequences within the human and other genomes is less than was hitherto expected. The c-kit quadruplex may be a new target for therapeutic intervention in cancers where there is elevated expression of the c-kit gene.
authors.affiliation: Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rankin
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Reszka
authors.forename: Julian
authors.initials: J
authors.lastname: Huppert
authors.forename: Mire
authors.initials: M
authors.lastname: Zloh
authors.forename: Gary N
authors.initials: GN
authors.lastname: Parkinson
authors.forename: Alan K
authors.initials: AK
authors.lastname: Todd
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladame
authors.forename: Shankar
authors.initials: S
authors.lastname: Balasubramanian
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D054856:G-Quadruplexes; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009857:Oncogenes / Q000235:genetics; D011401:Promoter Regions, Genetic; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D004247:DNA; D019009:Proto-Oncogene Proteins c-kit