Ssu72 phosphatase is a conserved telomere replication terminator.

Autor: Escandell JM; Instituto Gulbenkian de Ciência, Oeiras, Portugal jplanells@igc.gulbenkian.pt Miguel-Godinho.FERREIRA@unice.fr., Carvalho ES; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Gallo-Fernandez M; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Reis CC; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Matmati S; Equipe Labellisée Ligue, CRCM, CNRS, Inserm, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France., Luís IM; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal., Abreu IA; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal., Coulon S; Equipe Labellisée Ligue, CRCM, CNRS, Inserm, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France., Ferreira MG; Instituto Gulbenkian de Ciência, Oeiras, Portugal jplanells@igc.gulbenkian.pt Miguel-Godinho.FERREIRA@unice.fr.; Institute for Research on Cancer and Aging of Nice (IRCAN), INSERM U1081 UMR7284, CNRS, Nice, France.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2019 Apr 01; Vol. 38 (7). Date of Electronic Publication: 2019 Feb 21.
DOI: 10.15252/embj.2018100476
Abstrakt: 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.
(© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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