The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics.
MYC is deregulated in most tumour types, but an effective means to selectively target its aberrant expression is not yet available. Supercoiling that is induced by transcription has been demonstrated to have dynamic effects on DNA in the MYC promoter element: it converts duplex DNA to non-duplex DNA structures, even at considerable distances from the transcriptional start site. These non-duplex DNA structures, which control both turning on and off of transcription and the rate of transcription firing, are amenable to small-molecule targeting. This dynamic system provides a unique opportunity for the treatment of tumours in which MYC is an important oncogene.
Brooks
Tracy A
TA
College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Hurley
Laurence H
LH
D004278:DNA, Superhelical; D016503:Drug Delivery Systems; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics
D004278:DNA, Superhelical; D016271:Proto-Oncogene Proteins c-myc