Figure 2.

Possible relationships between t-loops and G-quadruplex structures. Top left: schematic of a t-loop formed by intercalation of a telomeric 3′ overhang into the duplex portion of a telomere; it is also possible for the other strand to participate in stabilizing the junction [81]. It is possible that G-quadruplexes could form in the displaced G-strand (the “D-loop”), or involving the 3′ overhang at the junction (not shown). It has been shown that RNA transcribed from telomeres (TERRA; green) localizes to the t-loop junction, possibly through DNA-RNA G-quadruplex formation [81]. Bottom left: electron microscopy image of a t-loop in genomic DNA isolated from human HeLa cells; image by Jack D. Griffith. Top right: it is possible that G-quadruplexes form at the telomeric overhang at times in the cell cycle when t-loops are resolved, although there is no direct evidence for this at present. Bottom right: Electron micrograph showing G-quadruplex formation in a long single-stranded telomeric fragment; image by Jack D. Griffith. Arrows indicate bead-like structures that represent higher-order interactions between multiple G-quadruplexes [82]. Figure created with BioRender.com.