Ssu72 phosphatase is a conserved telomere replication terminator

EMBO J. 2019 Apr 1;38(7):e100476. doi: 10.15252/embj.2018100476. Epub 2019 Feb 21.


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.

Keywords: CST; SSU72; fission yeast; lagging‐strand synthesis; telomere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / genetics
  • Conserved Sequence
  • DNA Replication*
  • Evolution, Molecular*
  • Humans
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoric Monoester Hydrolases / genetics*
  • Phosphorylation
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / genetics*
  • Sequence Homology
  • Telomere / genetics*
  • Telomere Homeostasis*


  • Carrier Proteins
  • Schizosaccharomyces pombe Proteins
  • Phosphoprotein Phosphatases
  • SSU72 protein, human
  • ssu72 protein, S pombe
  • Phosphoric Monoester Hydrolases