- Telomeres are repetitive nucleotide sequences located at the ends of linear eukaryotic chromosomes. In humans, the sequence consists of tandem repeats of the hexanucleotide TTAGGG, extending several kilobases in length.
- Telomeres function primarily to protect the structural integrity of chromosomes by preventing chromosomal ends from being mistaken for DNA double-strand breaks, which would otherwise trigger repair mechanisms that could lead to chromosomal fusions, rearrangements, or degradation. Along with their associated proteins, collectively known as the shelterin complex, telomeres form specialized nucleoprotein structures that safeguard genomic stability.
- During each round of DNA replication, the conventional DNA polymerase machinery is unable to fully replicate the 3′ ends of linear chromosomes due to the end-replication problem. As a result, telomeres progressively shorten with each cell division in most somatic cells. This gradual shortening acts as a biological clock that limits the number of times a cell can divide, contributing to the phenomenon known as the Hayflick limit.
- When telomeres reach a critically short length, they lose their protective function and elicit a DNA damage response, leading to replicative senescence or apoptosis, depending on the cellular context. This process is a key tumor-suppressive mechanism that helps prevent the unchecked proliferation of damaged or aged cells.
- To counteract telomere shortening, certain cell types express telomerase, a ribonucleoprotein enzyme that adds telomeric repeats to chromosome ends. Telomerase consists of two essential components: the catalytic subunit TERT (telomerase reverse transcriptase) and the RNA component TERC, which serves as a template for telomere elongation. In humans, telomerase is active in germline cells, embryonic stem cells, activated lymphocytes, and some adult stem cells, allowing these cells to maintain telomere length and proliferative capacity. In contrast, most somatic cells have little or no telomerase activity, leading to gradual telomere erosion with age.
- In many cancers, telomerase reactivation is a critical step in malignant transformation. Approximately 85–90% of human tumors upregulate telomerase, enabling cells to bypass senescence and become immortalized. The remaining tumors often utilize an alternative mechanism known as Alternative Lengthening of Telomeres (ALT), which relies on homologous recombination to maintain telomere length. These adaptations highlight the central role of telomere maintenance in the development and progression of cancer, and telomerase has become a target of interest for cancer therapeutics.
- Beyond cancer and aging, telomere biology is also implicated in a range of telomere-related disorders, collectively called telomeropathies or telomere syndromes. These include diseases such as dyskeratosis congenita, idiopathic pulmonary fibrosis, aplastic anemia, and some forms of liver cirrhosis, all of which are associated with abnormally short telomeres and impaired regenerative capacity. Measuring telomere length has thus emerged as a potential biomarker for cellular aging, disease risk, and biological stress.
