Schematic representation of telomere structure. Telomeres are at the extremities of chromosome DNA. The telomeric 3′ end terminates as a single-stranded, G-rich overhang able to form the t-loop, in which the overhang invades the telomeric double helix, remodeling the DNA into a circle. Telomeres are capped by at least 6 proteins (TRF1, TRF2, TPP1, POT1, TIN2, and Rap1), collectively known as shelterin, that physically shield the DNA.¹⁹  TRF1, TRF2, and TPP1 specifically recognize and bind to double-stranded TTAGGG repeats; POT1 binds to the single-stranded telomeric overhang^19,20 ; TIN2 and Rap1 complete the shelterin complex. Shelterin allows discrimination of telomeres from double-stranded DNA breaks; lack of shelterin allows telomeres to be identified as double-stranded DNA breaks and triggers DNA-damage pathways.¹⁹