telomerase

Telomerase is a ribonucleoprotein enzyme that maintains telomeres, the protective ends of chromosomes. In humans it consists of the catalytic reverse transcriptase subunit TERT and an RNA component TERC that provides a template for adding DNA repeats. The active enzyme adds TTAGGG repeats to the 3' ends of linear chromosomes, counteracting shortening during DNA replication.

Telomerase extends telomeres by reverse transcription of the RNA template, creating DNA repeats that serve as a buffer against progressive loss of telomeric DNA. The enzyme complex is recruited to telomeres by the shelterin protein complex and requires additional factors for assembly, localization, and RNA stability, including H/ACA small nucleolar RNA–protein components.

Telomerase activity is tightly regulated. In humans, TERT expression is low in most somatic cells but active in germ cells, stem cells, and certain proliferative tissues. Telomerase can be repressed by transcriptional and post-translational mechanisms and can be upregulated in cancer, contributing to cellular immortality. Telomere length and integrity influence cell cycle checkpoints and genome stability.

Clinical relevance: Telomerase is a target for cancer therapies; inhibitors such as imetelstat have been tested in clinical trials. Conversely, strategies to activate telomerase have been explored for aging and tissue regeneration, though risks include promoting oncogenesis. Some cancers maintain telomeres without telomerase via alternative lengthening of telomeres (ALT).

History: Telomerase was discovered in 1984 by Elizabeth Blackburn and Carol Greider in experiments with Tetrahymena. The discovery revealed how chromosome ends are preserved and earned the two researchers the Nobel Prize in Physiology or Medicine in 2009 (shared with Jack Szostak).