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

Ssu72 phosphatase is a conserved telomere replication terminator.

Author information

1
Instituto Gulbenkian de Ciência, Oeiras, Portugal jplanells@igc.gulbenkian.pt Miguel-Godinho.FERREIRA@unice.fr.
2
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
3
Equipe Labellisée Ligue, CRCM, CNRS, Inserm, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France.
4
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
5
Institute for Research on Cancer and Aging of Nice (IRCAN), INSERM U1081 UMR7284, CNRS, Nice, France.

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.

KEYWORDS:

CST ; SSU72; fission yeast; lagging‐strand synthesis; telomere

PMID:
30796050
PMCID:
PMC6443209
DOI:
10.15252/embj.2018100476
[Indexed for MEDLINE]
Free PMC Article

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