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Article Dans Une Revue EMBO Journal Année : 2019

Ssu72 phosphatase is a conserved telomere replication terminator

Résumé

Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions of conventional DNA poly-merases and elongated by telomerase, but the regulation of this process is not fully understood. Telomere replication requires (Ctc1/ Cdc13)-Stn1-Ten1, a telomeric ssDNA-binding complex homologous to RPA. Here, we show that the evolutionarily conserved phos-phatase 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 Ser74, a residue located within its conserved OB-fold domain. Consequently, ssu72Δ mutants are defective in telomere replication and exhibit long 3 0-ssDNA overhangs, indicative of defective lagging-strand DNA synthesis. We also show that hSSU72 regulates telomerase activation in human cells by controlling recruitment of hSTN1 to telomeres. These results reveal 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.
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Dates et versions

hal-02367274 , version 1 (17-11-2019)

Identifiants

Citer

Jose Miguel Escandell, Edison Sm Carvalho, Maria Gallo-Fernandez, Clara C Reis, Samah Matmati, et al.. Ssu72 phosphatase is a conserved telomere replication terminator. EMBO Journal, 2019, 38 (7), pp.e100476. ⟨10.15252/embj.2018100476⟩. ⟨hal-02367274⟩
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