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Reference - PMID:30796050 - Ssu72 phosphatase is a conserved telomere replication terminator.

Reference summary

PubMed ID
PMID:30796050
Title
Ssu72 phosphatase is a conserved telomere replication terminator.
Authors
Escandell JM, Carvalho ES, Gallo-Fernandez M, Reis CC, Matmati S, Luís IM, Abreu IA, Coulon S, Ferreira MG
Citation
EMBO J 2019 Apr 01;38(7)
Publication year
2019
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.

Annotation

GO biological process

GO:0032215 - positive regulation of telomere maintenance via semi-conservative replication

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GO cellular component

GO:0000785 - chromatin

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GO molecular function

GO:0004722 - protein serine/threonine phosphatase activity

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Modification

MOD:00046 - O-phospho-L-serine

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Multi-locus phenotype

FYPO:0003803 - decreased protein localization to telomere

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FYPO:0002019 - elongated telomeres during vegetative growth

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FYPO:0003107 - progressively shortening telomeres during vegetative growth

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Single locus phenotype

FYPO:0000705 - abolished protein-protein interaction

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FYPO:0006860 - decreased mitotic DNA replication at rDNA

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FYPO:0006859 - decreased mitotic DNA replication at telomere

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FYPO:0003803 - decreased protein localization to telomere

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FYPO:0002019 - elongated telomeres during vegetative growth

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FYPO:0004656 - increased protein localization to telomere during vegetative growth

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FYPO:0001038 - increased protein phosphorylation during vegetative growth

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FYPO:0005402 - increased telomeric 3' overhang length during vegetative growth

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FYPO:0000703 - normal protein-protein interaction

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Genotypes:

FYPO:0003107 - progressively shortening telomeres during vegetative growth

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Genotypes: