Physiological assembly and activity of human telomerase complexes

Telomerase is a specialized reverse transcriptase conserved throughout almost all eukaryotic life. It plays a fundamental role in genome maintenance, adding back the telomeric DNA repeats lost from chromosome ends due to incomplete replication or damage. The protein and RNA subunits of telomerase fold and function in a co-dependent manner to establish a high fidelity of telomeric repeat synthesis. Over the past two decades, studies of telomerase have uncovered previously unanticipated levels of complexity in its assembly, activity and regulation. This review describes the current understanding of telomerase in humans, with particular focus on telomerase biogenesis and regulation in its cellular context.