Targeting Promoter G-Quadruplexes for Transcriptional Control
Non-canonical DNA structures are found throughout the genome, transiently interspersed with B-DNA, in regions that are important for the regulation of various cellular processes. G–C-rich tracts, in particular, can form unique higher order G-quadruplex structures, which have been shown to exist in regions of DNA repair, telomeric regulation, centromeres and, most notably, transcriptional control. These structures have been identified in the promoters of an array of proto-oncogenes and represent attractive targets for small molecule development. This chapter focuses on the identification and targeting of G-quadruplex structures found in telomeres and oncogenes, discusses the findings related to the transcriptional regulation of MYC, kRAS, and Bcl-2, and concludes with a discussion on the future of targeting unique G-quadruplexes throughout the genome.