The linearity of chromosomes creates two major problems for eukaryotic cells: the end replication problem and the end protection problem. The former stems from the inherent inability of the replication machinery to fully duplicate linear templates. The latter refers to the propensity of linear chromosome ends to be recognized as DNA double stranded breaks. To surmount both problems, cells use telomeres, the specific nucleoprotein complexes that are essential to ensure genomic stability and promote cellular survival.

In mammalian cells, telomeres consist of tracts of repetitive DNA sequences (TTAGGG) that ranges in size from ~10 kilobases in primates and other long-lived animals, to >50 kilobases in short lived animals including rodents. Telomeric DNA is bound by a specialized set of proteins whose composition, structure, and function have diverged across species. In mammalian cells, the bona fide telomere specific proteins are six- TRF1, TRF2, Rap1, TIN2, TPP1 and POT1, which together form a complex termed shelterin. Shelterin forms the basis of the solution to the end-protection problem and inhibits the various DNA damage signaling and repair pathways at chromosome ends.

Telomeric DNA is replenished by telomerase, a reverse transcriptase that is expressed during the early stages of embryonic development and subsequently repressed in all cells except for germ cells and stem cells. Normal human somatic cells lack the activity of telomerase and gradually loose telomeric repeats during progressive division cycles until they ultimately undergo cellular senescence. The vast majority of cancer cells overcome the senescence barrier by reactivating telomerase.