telomerase

Telomerase (also called TERT, telomerase reverse transcriptase, when referring to its catalytic subunit) uses an internal RNA template (TERC) to synthesize telomeric DNA repeats onto chromosome ends, compensating for the 'end-replication problem' caused by the inability of DNA polymerase to fully replicate the lagging strand at the 3' end of linear chromosomes. Without telomerase, telomeres progressively shorten with each cell division, eventually triggering replicative senescence (Hayflick limit) or apoptosis when telomeres become critically short, activating p53-mediated DNA damage responses. Most normal somatic cells have low or no telomerase activity, limiting their replicative capacity, whereas germ cells, embryonic stem cells, and hematopoietic stem cells maintain telomerase activity to preserve proliferative potential. Clinically, telomerase reactivation is a hallmark of cancer (~90% of cancers show upregulated telomerase), allowing malignant cells to bypass senescence and achieve immortalization—making telomerase a target for anticancer drug development (e.g., telomerase inhibitors). Conversely, loss-of-function mutations in telomerase components (TERT, TERC, dyskerin) cause telomere biology disorders such as dyskeratosis congenita, characterized by bone marrow failure, pulmonary fibrosis, and premature aging phenotypes due to accelerated telomere attrition. Telomerase activity is also of interest in aging research, as it is proposed to counteract cellular senescence associated with organismal aging.