The DNA secondary structures at telomeres and genome instability

Abstract

Telomeric DNA are TTAGGG tandem repeats, which are susceptible for oxidative DNA damage and hotspot regions for formation of DNA secondary structures such as t-loop, D-loop, G-quadruplexes (G4), and R-loop. In the past two decades, unique DNA or RNA secondary structures at telomeres or some specific regions of genome have become promising therapeutic targets. G-quadruplex and R-loops at telomeres or transcribed regions of genome have been considered as the potential targets for cancer therapy. Here we discuss the potentials to target the secondary structures (G4s and R-loops) in genome as therapy approaches.

Keywords: G-quadruplexes; R-loop; Secondary structures; Telomere; Therapy; Transcription.

Fig. 1

Targeting G-quadruplex structures in telomerase positive or ALT cancer cells. Left: unresolved G4s block the function of telomerase for telomere elongation in telomerase positive cells; Middle: stabilized G4s at some oncogene promoters lead to the repression of those oncogenes; Right: Targeting G-loop with G4s ligands or R-loop inhibitors may be a potential therapeutics for ALT cancers