biostudies-literatureUnknownCai SWNCI NIH HHSTelomere maintenance requires extension of the G-rich telomeric repeat strand by telomerase and fill-in synthesis of the C-rich strand by Polα/Primase. Telomeric Polα/Primase is bound to Ctc1-Stn1-Ten1 (CST), a single-stranded DNA-binding complex. Like mutations in telomerase, mutations affecting CST-Polα/Primase result in pathological telomere shortening and cause a telomere biology disorder, Coats plus (CP). We determined cryogenic electron microscopy structures of human CST bound to the shelterin heterodimer POT1/TPP1 that reveal how CST is recruited to telomeres by POT1. Phosphorylation of POT1 is required for CST recruitment, and the complex is formed through conserved interactions involving several residues mutated in CP. Our structural and biochemical data suggest that phosphorylatebioRxiv : the preprint server for biology2023.05.08.539880https://www.ebi.ac.uk/biostudies/studies/S-EPMC10197580biostudies-literaturePOT1 recruits and regulates CST-Polα/Primase at human telomeres.PMC10197580R35 CA210036R50 CA243771Cai SWWalz TTakai Hde Lange TfalsePOT1 recruits and regulates CST-Polα/Primase at human telomeres.Telomere maintenance requires extension of the G-rich telomeric repeat strand by telomerase and fill-in synthesis of the C-rich strand by Polα/Primase. Telomeric Polα/Primase is bound to Ctc1-Stn1-Ten1 (CST), a single-stranded DNA-binding complex. Like mutations in telomerase, mutations affecting CST-Polα/Primase result in pathological telomere shortening and cause a telomere biology disorder, Coats plus (CP). We determined cryogenic electron microscopy structures of human CST bound to the shelterin heterodimer POT1/TPP1 that reveal how CST is recruited to telomeres by POT1. Phosphorylation of POT1 is required for CST recruitment, and the complex is formed through conserved interactions involving several residues mutated in CP. Our structural and biochemical data suggest that phosphorylate2023-01-01T00:00:00Z2023 Oct2026-04-08T14:39:42.741Z2025-04-04T11:50:11.358ZS-EPMC101975803721500510.1101/2023.05.08.539880