PT - JOURNAL ARTICLE AU - Escandell, Jose Miguel AU - Carvalho, Edison S. Mascarenhas AU - Gallo-Fernandez, Maria AU - Reis, Clara C. AU - Matmati, Samah AU - Luís, Inês Matias AU - Abreu, Isabel A. AU - Coulon, Stéphane AU - Ferreira, Miguel Godinho TI - SSU72 phosphatase is a telomere replication terminator AID - 10.1101/382564 DP - 2018 Jan 01 TA - bioRxiv PG - 382564 4099 - http://biorxiv.org/content/early/2018/08/01/382564.short 4100 - http://biorxiv.org/content/early/2018/08/01/382564.full AB - Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions by conventional DNA polymerases and telomerase, though the regulation of this process is not fully understood. Telomere replication requires (C)-Stn1-Ten1, a telomere ssDNA-binding complex that is homologous to RPA. Here, we show that the evolutionarily conserved phosphatase Ssu72 is responsible for terminating the cycle of telomere replication in fission yeast. Ssu72 controls the recruitment of Stn1 to telomeres by regulating Stn1 phosphorylation at S74, a residue that lies within the conserved OB fold domain. Consequently, ssu72Δ mutants are defective in telomere replication and exhibit long 3’ overhangs, which are indicative of defective lagging strand DNA synthesis. We also show that hSSU72 regulates telomerase activation in human cells by controlling the recruitment of hSTN1 to telomeres. Thus, in this study, we demonstrate a previously unknown yet conserved role for the phosphatase SSU72, whereby this enzyme controls telomere homeostasis by activating lagging strand DNA synthesis, thus terminating the cycle of telomere replication.