Figure 2.

Telomeres act as protective caps at the end of chromosomes. They consist of a sequence of 6 nucleotides (G-strand: 5′-TTAGGG-3′; C-strand: 3′-AATCCC-5′) repeated several thousand times. Telomeres loses length with each cell division. To prevent excessive shortening, they are protected by shelterin. Shelterin is a protein complex consisting of six subunits: telomere repeat binding factor 1 (TRF1), telomere repeat binding factor 2 (TRF2), protection of telomere 1 (POT1), repressor/activator protein 1 (RAP1), TRF1- and TRF2-interacting nuclear protein 2 (TIN2) and tripeptidyl peptidase 1 (TPP1). The 3’ end of the G-rich strand extends over the end of the C-rich strand (5’ end) of the telomere. Given sufficient length of the telomere, this forms the t-loop, which overlaps with the double-stranded 5’ end, building the D-loop protecting the telomeres (c). During replication, the G- and C-strands are open. Telomerase can bind to the G-strand to add telomeric repeats preventing the cell from damage (b). Loss of function and degradation of the shelterin complex leading to DNA damage occur more frequently during aging and cause the cell to stop dividing (a).