Ssu72 phosphatase is a conserved telomere replication terminator

Jose Miguel Escandell, Edison S.M. Carvalho, Maria Gallo-Fernandez, Clara C. Reis, Samah Matmati, Inês Matias Luís, Isabel A. Abreu, Stéphane Coulon, Miguel Godinho Ferreira

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions of conventional DNA polymerases 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 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 Ser74, a residue located within its conserved OB-fold domain. Consequently, ssu72∆ mutants are defective in telomere replication and exhibit long 3′-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.

Original languageEnglish
Article numbere100476
JournalEmbo Journal
Volume38
Issue number7
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • CST
  • fission yeast
  • lagging-strand synthesis
  • SSU72
  • telomere

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