- Telomerase is a specialized ribonucleoprotein reverse transcriptase that plays a critical role in maintaining telomere length at the ends of linear chromosomes in eukaryotic cells.
- Telomeres are repetitive DNA sequences (e.g., TTAGGG in humans) that protect chromosomal ends from degradation, recombination, and recognition as DNA damage.
- During DNA replication, the inability of conventional DNA polymerases to fully replicate the 3′ ends of linear DNA—known as the end-replication problem—leads to progressive telomere shortening with each cell division. Telomerase counteracts this shortening by adding telomeric repeats, thereby contributing to chromosomal stability and cellular longevity.
- Structurally, telomerase is composed of two core components:
- Telomerase reverse transcriptase (TERT) – the catalytic protein subunit that synthesizes DNA from an RNA template.
- Telomerase RNA component (TERC or TR) – an intrinsic RNA molecule that serves as the template for adding telomeric repeats.
- The enzyme functions by binding to the 3′ single-stranded overhang of telomeric DNA and extending it using TERC as a guide. Once a telomeric repeat is added, the enzyme translocates and adds another repeat, allowing for multiple rounds of extension. The complementary strand is then synthesized by conventional DNA polymerases.
- Telomerase is highly active in germ cells, embryonic stem cells, and certain adult stem cell populations, where long-term proliferative capacity is required. In contrast, most somatic cells exhibit low or undetectable telomerase activity, leading to gradual telomere shortening and eventual replicative senescence or apoptosis—a key mechanism in aging and tumor suppression.
- Importantly, reactivation of telomerase is observed in over 85% of human cancers, where it enables cells to bypass senescence and achieve replicative immortality. This makes telomerase a major target in anti-cancer drug development, either by directly inhibiting its enzymatic function or interfering with its expression and assembly.
- In conclusion, telomerase is an essential enzyme for preserving genome integrity and regulating cellular lifespan through the maintenance of telomeres. While vital for development and tissue renewal, its dysregulation is closely associated with oncogenesis, aging-related pathologies, and stem cell biology.
