Fig. 1

Schematic representation of telomeric DNA and components of the shelterin complex. Telomeres comprise a specialized nucleoprotein-capping structure consisting of DNA and shelterin protein complexes. Telomeric DNA contains a variable number of G-rich, non-coding, tandem repeats of the double-stranded DNA sequence 5′-(TTAGGG) _n -3′, followed by a terminal 3′ G-rich single-stranded overhang (150–200 nucleotides (nt) long). The 3′ G-rich overhang facilitates telomeric DNA in forming a higher-order structure in which the 3′ single-stranded overhang folds back and invades the homologous double-stranded TTAGGG region, forming a telomeric loop (T-loop) that provides 3′-end protection by sequestering it from recognition by the DNA damage response machinery. The proteins associated with telomeres form the shelterin complex, which consists of three core shelterin subunits, TRF1 and TRF2, which directly recognize and bind duplex TTAGGG repeats, and POT1, which recognizes and binds single-stranded TTAGGG overhangs. These three proteins are interconnected by three additional shelterin proteins, TIN2, TPP1 and RAP1, forming a complex that enables the DNA damage response surveillance machinery to distinguish telomere DNA from sites of genomic DNA damage