Rankin Sarah, Reszka Anthony P, Huppert Julian, Zloh Mire, Parkinson Gary N, Todd Alan K, Ladame Sylvain, Balasubramanian Shankar, Neidle Stephen
Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
J Am Chem Soc. 2005 Aug 3;127(30):10584-9. doi: 10.1021/ja050823u.
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.
DNA序列d(AGGGAGGGCGCTGGGAGGAGGG)存在于原癌基因c-kit的启动子区域内。我们在此表明，通过结合核磁共振（NMR）、圆二色性和熔解温度测量，该序列在生理条件下形成四链体结构。已经研究了鸟嘌呤束之间插入序列的变化，令人惊讶的是，在这些条件下，这些修饰序列中没有一个形成四链体排列。这表明在人类和其他基因组中形成四链体的序列的出现频率低于迄今为止的预期。c-kit四链体可能是对c-kit基因表达升高的癌症进行治疗干预的新靶点。
