Ssu72 Phosphatase is a Conserved Telomere Replication Terminator

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2019 Feb 24

PMID 30796050

Citations 9

Authors

Jose Miguel Escandell

Edison Sm Carvalho

Maria Gallo-Fernandez

Clara C Reis

Samah Matmati

Ines Matias Luis

Isabel A Abreu

Stephane Coulon

Miguel Godinho Ferreira

Affiliations

Soon will be listed here.

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, 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.

Citing Articles

Ssu72: a versatile protein with functions in transcription and beyond.

Fidler E, Dwyer K, Ansari A Front Mol Biosci. 2024; 11:1332878.

PMID: 38304578 PMC: 10830811. DOI: 10.3389/fmolb.2024.1332878.

Pot1 promotes telomere DNA replication via the Stn1-Ten1 complex in fission yeast.

Carvalho Borges P, Bouabboune C, Escandell J, Matmati S, Coulon S, Ferreira M Nucleic Acids Res. 2023; 51(22):12325-12336.

PMID: 37953281 PMC: 10711446. DOI: 10.1093/nar/gkad1036.

A proto-telomere is elongated by telomerase in a shelterin-dependent manner in quiescent fission yeast cells.

Vaurs M, Audry J, Runge K, Geli V, Coulon S Nucleic Acids Res. 2022; 50(20):11682-11695.

PMID: 36330920 PMC: 9723628. DOI: 10.1093/nar/gkac986.

Hypophosphorylated pRb knock-in mice exhibit hallmarks of aging and vitamin C-preventable diabetes.

Jiang Z, Li H, Schroer S, Voisin V, Ju Y, Pacal M EMBO J. 2022; 41(4):e106825.

PMID: 35023164 PMC: 8844977. DOI: 10.15252/embj.2020106825.

Fission yeast Stn1 maintains stability of repetitive DNA at subtelomere and ribosomal DNA regions.

Yamamoto I, Nakaoka H, Takikawa M, Tashiro S, Kanoh J, Miyoshi T Nucleic Acids Res. 2021; 49(18):10465-10476.

PMID: 34520548 PMC: 8501966. DOI: 10.1093/nar/gkab767.

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