Putative DNA quadruplex formation within the human c-kit oncogene.
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.
Rankin
Sarah
S
Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Reszka
Anthony P
AP
Huppert
Julian
J
Zloh
Mire
M
Parkinson
Gary N
GN
Todd
Alan K
AK
Ladame
Sylvain
S
Balasubramanian
Shankar
S
Neidle
Stephen
S
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*
D004247:DNA; D019009:Proto-Oncogene Proteins c-kit