telomer

Telomere is the repetitive nucleotide sequence at the ends of linear chromosomes that protects chromosome termini from deterioration and from being mistaken for DNA breaks. This protection prevents end-to-end fusions and helps maintain genomic stability. In humans, telomeric DNA consists of tandem repeats of the sequence TTAGGG, extending several kilobases at chromosome ends, though length varies by tissue and age. The telomere is bound by the shelterin protein complex, which includes TRF1, TRF2, POT1, TIN2, TPP1, and RAP1. Shelterin promotes a t-loop structure in which the single-stranded overhang invades the double-stranded telomeric DNA, concealing the terminus from DNA damage sensors.

Replication of linear DNA cannot fully copy chromosome ends, leading to progressive shortening with each cell division. Telomerase, a ribonucleoprotein enzyme comprising the reverse transcriptase TERT and an RNA component TERC, adds telomeric repeats to the 3' end, counteracting shortening. Telomerase activity is high in germ cells, stem cells, and some immune cells, but low or absent in most somatic cells. In many cancers, telomerase is reactivated, contributing to cellular immortality. A subset of cancers maintains telomeres via an alternative lengthening of telomeres (ALT) mechanism that relies on recombination rather than telomerase.

Biological significance and clinical relevance include the role of telomeres in aging, as critically short telomeres can trigger senescence or apoptosis. Telomere biology defects underlie disorders such as dyskeratosis congenita. Telomere length serves as a research biomarker for aging and disease, though influenced by genetics and environmental factors.