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The nucleolar protein GNL3 prevents resection of stalled replication forks.
Lebdy, Rana; Canut, Marine; Patouillard, Julie; Cadoret, Jean-Charles; Letessier, Anne; Ammar, Josiane; Basbous, Jihane; Urbach, Serge; Miotto, Benoit; Constantinou, Angelos; Abou Merhi, Raghida; Ribeyre, Cyril.
Afiliación
  • Lebdy R; Institut de Génétique Humaine (UMR9002), CNRS, Université de Montpellier, Montpellier Cedex 5, France.
  • Canut M; Faculty of Sciences, Genomics and Surveillance Biotherapy (GSBT) Laboratory, R. Hariri Campus, Lebanese University, Hadath, Lebanon.
  • Patouillard J; Institut de Génétique Humaine (UMR9002), CNRS, Université de Montpellier, Montpellier Cedex 5, France.
  • Cadoret JC; Institut de Génétique Humaine (UMR9002), CNRS, Université de Montpellier, Montpellier Cedex 5, France.
  • Letessier A; Université Paris Cité, CNRS, Institut Jacques Monod, Paris, France.
  • Ammar J; Université Paris Cité, Institut Cochin, INSERM, CNRS, Paris, France.
  • Basbous J; Institut de Génétique Humaine (UMR9002), CNRS, Université de Montpellier, Montpellier Cedex 5, France.
  • Urbach S; Institut de Génétique Humaine (UMR9002), CNRS, Université de Montpellier, Montpellier Cedex 5, France.
  • Miotto B; Institut de Génomique Fonctionnelle, CNRS UMR 5203, Inserm U1191, Université de Montpellier, Montpellier Cedex 5, France.
  • Constantinou A; Université Paris Cité, Institut Cochin, INSERM, CNRS, Paris, France.
  • Abou Merhi R; Institut de Génétique Humaine (UMR9002), CNRS, Université de Montpellier, Montpellier Cedex 5, France.
  • Ribeyre C; Faculty of Sciences, Genomics and Surveillance Biotherapy (GSBT) Laboratory, R. Hariri Campus, Lebanese University, Hadath, Lebanon.
EMBO Rep ; 24(12): e57585, 2023 Dec 06.
Article en En | MEDLINE | ID: mdl-37965896
Faithful DNA replication requires specific proteins that protect replication forks and so prevent the formation of DNA lesions that may damage the genome. Identification of new proteins involved in this process is essential to understand how DNA lesions accumulate in cancer cells and how they tolerate them. Here, we show that human GNL3/nucleostemin, a GTP-binding protein localized mostly in the nucleolus and highly expressed in cancer cells, prevents nuclease-dependent resection of nascent DNA in response to replication stress. We demonstrate that inhibiting origin firing reduces resection. This suggests that the heightened replication origin activation observed upon GNL3 depletion largely drives the observed DNA resection probably due to the exhaustion of the available RPA pool. We show that GNL3 and DNA replication initiation factor ORC2 interact in the nucleolus and that the concentration of GNL3 in the nucleolus is required to limit DNA resection. We propose that the control of origin firing by GNL3 through the sequestration of ORC2 in the nucleolus is critical to prevent nascent DNA resection in response to replication stress.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Proteínas de Unión al GTP / Replicación del ADN Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Proteínas de Unión al GTP / Replicación del ADN Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article