Abstract
The purpose of the study was to elucidate how DNA tetraplex (also referred to as G-quadruplex)-forming oligonucleotides mediate suppression of the human c-myc gene at the level of transcription initiation. A 22-base-long oligonucleotide, which is rich in guanines and folds into an intrastrand DNA tetraplex under physiological conditions, was administered to a Burkitt's lymphoma cell line overexpressing a (8:14) translocated c-myc allele. Administration of the oligonucleotide at nanomolar concentrations to the surrounding medium resulted in efficient cellular uptake, and was accompanied by a substantial concentration- and conformation-dependent decrease in growth rate. We discuss how c-myc transcription is initiated at the molecular level and speculate that the oligonucleotide exerts a dual effect on c-myc expression in vivo.
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