Putative DNA quadruplex formation within the human c-kit oncogene.

Rankin, S., Reszka, A.P., Huppert, J., Zloh, M., Parkinson, G.N., Todd, A.K., Ladame, S., Balasubramanian, S. and Neidle, S. (2005) Putative DNA quadruplex formation within the human c-kit oncogene. Journal of the American Chemical Society, 127 . pp. 10584-10589. 10.1021/ja050823u.

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DOI: 10.1021/ja050823u

Abstract

Putative DNA Quadruplex Formation within the Human c-kit Oncogene Sarah Rankin, Anthony P. Reszka, Julian Huppert, Mire Zloh, Gary N. Parkinson, Alan K. Todd, Sylvain Ladame, Shankar Balasubramanian, and Stephen Neidle* Contribution from the Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK, and University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK stephen.neidle@ulsop.ac.uk Received February 8, 2005 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.

Item Type:Article
Additional Information:Full text available in print and electronically from the School of Pharmacy Library.
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:883
Journal or Publication Title:Journal of the American Chemical Society
Deposited By:Library Staff
Deposited On:04 Mar 2008 11:08
Last Modified:20 Jan 2012 17:39

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