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Telomerase is a ribonucleoprotein enzyme responsible for maintaining the length of telomeres by adding guanine-rich repetitive sequences to the ends of chromosomes. It plays a crucial role in genome stability. The enzyme consists of a catalytic protein subunit, Telomerase Reverse Transcriptase (TERT), which functions as a reverse transcriptase, and a non-coding RNA component (TERC/TR) that contains the template for synthesis. Telomerase is typically active in germ cells and rapidly dividing cells like stem cells and tumor cells, but generally not in normal somatic cells. Reactivation of telomerase is a hallmark of most human cancers, contributing to unlimited cell proliferation. Mutations or dysregulation of telomerase components are also associated with diseases like bone marrow failure syndromes and telomere-related disorders, including premature aging syndromes. Due to its role in cancer and other diseases, telomerase is considered an important therapeutic target.
Telomerase is recruited to the telomere by proteins like TPP1. It uses its RNA template (TERC) to bind to the chromosome end and add a specific repeat sequence (5'-GGTTAG-3' in humans) to the 3' strand. After adding a repeat, the enzyme releases, realigns the new 3'-end to the template, and repeats the process, effectively extending the telomere and counteracting the shortening that occurs during DNA replication.
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