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. Vari...

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Veröffentlicht in:Journal of the American Chemical Society 2005-08, Vol.127 (30), p.10584-10589
Hauptverfasser: Rankin, Sarah, Reszka, Anthony P, Huppert, Julian, Zloh, Mire, Parkinson, Gary N, Todd, Alan K, Ladame, Sylvain, Balasubramanian, Shankar, Neidle, Stephen
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container_end_page 10589
container_issue 30
container_start_page 10584
container_title Journal of the American Chemical Society
container_volume 127
creator Rankin, Sarah
Reszka, Anthony P
Huppert, Julian
Zloh, Mire
Parkinson, Gary N
Todd, Alan K
Ladame, Sylvain
Balasubramanian, Shankar
Neidle, Stephen
description 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.
doi_str_mv 10.1021/ja050823u
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source MEDLINE; ACS Publications
subjects Base Sequence
Biological and medical sciences
Circular Dichroism
DNA - chemistry
DNA - genetics
DNA - metabolism
Fundamental and applied biological sciences. Psychology
G-Quadruplexes
Humans
Molecular biophysics
Nuclear Magnetic Resonance, Biomolecular
Oncogenes - genetics
Promoter Regions, Genetic
Proto-Oncogene Proteins c-kit - genetics
Structure in molecular biology
Supramolecular structure
title Putative DNA Quadruplex Formation within the Human c-kit Oncogene
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