1. Ssu72 phosphatase is a conserved telomere replication terminator
- Author
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Maria Gallo-Fernandez, Clara C. Reis, Edison S. M. Carvalho, Samah Matmati, Inês M. Luís, Isabel A. Abreu, José M. Escandell, Miguel Godinho Ferreira, Stéphane Coulon, Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Institute for Research on Cancer and Aging of Nice (IRCAN)
- Subjects
Telomerase ,DNA polymerase ,Sequence Homology ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,0302 clinical medicine ,Phosphoprotein Phosphatases ,Phosphorylation ,ComputingMilieux_MISCELLANEOUS ,Conserved Sequence ,0303 health sciences ,telomere ,biology ,General Neuroscience ,lagging‐strand synthesis ,Articles ,fission yeast ,Cell biology ,Terminator (genetics) ,lagging-strand synthesis ,DNA Replication ,SSU72 ,Phosphatase ,General Biochemistry, Genetics and Molecular Biology ,Article ,Evolution, Molecular ,03 medical and health sciences ,Telomere Homeostasis ,Schizosaccharomyces ,Homologous chromosome ,Humans ,Proteolysis & Proteomics ,Amino Acid Sequence ,Molecular Biology ,030304 developmental biology ,CST ,General Immunology and Microbiology ,DNA synthesis ,DNA Replication, Repair & Recombination ,Post-translational Modifications, Proteolysis & Proteomics ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Phosphoric Monoester Hydrolases ,Telomere ,telomere Subject Categories DNA Replication ,biology.protein ,Repair & Recombination ,Schizosaccharomyces pombe Proteins ,Carrier Proteins ,030217 neurology & neurosurgery ,Post-translational Modifications - Abstract
International audience; Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions of conventional DNA poly-merases 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 phos-phatase 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, ssu72Δ mutants are defective in telomere replication and exhibit long 3 0-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.
- Published
- 2019
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