Fig. 3

Telomerase assembly, recruitment to the telomere, and telomeric DNA synthesis. Telomerase is the cellular ribonucleoprotein enzyme complex that catalyzes the extension of telomeric DNA in eukaryotic organisms. Telomerase action involves multiple steps including assembly of the telomerase complex, its intracellular trafficking and finally recruitment to telomeres. Human telomerase is composed of hTR (hTERC—a template functional RNA), hTERT (the catalytic protein component with reverse transcriptase activity), and the accessory proteins dyskerin, NOP10, NHP2, and GAR1. hTERT protein associates with p23 and HSP90 in the cytoplasm, and moves to the nucleus. Nascent hTR transcripts complex with dyskerin, NHP2, NOP10 and GAR1. This complex then undergoes Reptin and Pontin (ATPases)-mediated binding to hTERT + p23 + HSP90 complex. Then TCAB1 attaches to this assembling complex and guides it to Cajal bodies in the nucleus. Telomerase recruitment to telomeres takes place during the S phase of the cell cycle through interactions between the shelterin complex components TPP1 and POT1 and the DAT domain of hTERT. SRSF11 stabilizes the association of the telomerase enzyme complex with the telomere overhang for DNA synthesis