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Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair

Cells are constantly threatened by multiple sources of genotoxic stress that cause DNA damage. To maintain genome integrity, cells have developed a coordinated signalling network called DNA damage response (DDR). While multiple kinases have been thoroughly studied during DDR activation, the role of...

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Autores principales: Villoria, María Teresa, Ramos, Facundo, Dueñas, Encarnación, Faull, Peter, Cutillas, Pedro Rodríguez, Clemente‐Blanco, Andrés
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210157/
https://www.ncbi.nlm.nih.gov/pubmed/27852625
http://dx.doi.org/10.15252/embj.201593540
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author Villoria, María Teresa
Ramos, Facundo
Dueñas, Encarnación
Faull, Peter
Cutillas, Pedro Rodríguez
Clemente‐Blanco, Andrés
author_facet Villoria, María Teresa
Ramos, Facundo
Dueñas, Encarnación
Faull, Peter
Cutillas, Pedro Rodríguez
Clemente‐Blanco, Andrés
author_sort Villoria, María Teresa
collection PubMed
description Cells are constantly threatened by multiple sources of genotoxic stress that cause DNA damage. To maintain genome integrity, cells have developed a coordinated signalling network called DNA damage response (DDR). While multiple kinases have been thoroughly studied during DDR activation, the role of protein dephosphorylation in the damage response remains elusive. Here, we show that the phosphatase Cdc14 is essential to fulfil recombinational DNA repair in budding yeast. After DNA double‐strand break (DSB) generation, Cdc14 is transiently released from the nucleolus and activated. In this state, Cdc14 targets the spindle pole body (SPB) component Spc110 to counterbalance its phosphorylation by cyclin‐dependent kinase (Cdk). Alterations in the Cdk/Cdc14‐dependent phosphorylation status of Spc110, or its inactivation during the induction of a DNA lesion, generate abnormal oscillatory SPB movements that disrupt DSB‐SPB interactions. Remarkably, these defects impair DNA repair by homologous recombination indicating that SPB integrity is essential during the repair process. Together, these results show that Cdc14 promotes spindle stability and DSB‐SPB tethering during DNA repair, and imply that metaphase spindle maintenance is a critical feature of the repair process.
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spelling pubmed-52101572017-01-05 Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair Villoria, María Teresa Ramos, Facundo Dueñas, Encarnación Faull, Peter Cutillas, Pedro Rodríguez Clemente‐Blanco, Andrés EMBO J Articles Cells are constantly threatened by multiple sources of genotoxic stress that cause DNA damage. To maintain genome integrity, cells have developed a coordinated signalling network called DNA damage response (DDR). While multiple kinases have been thoroughly studied during DDR activation, the role of protein dephosphorylation in the damage response remains elusive. Here, we show that the phosphatase Cdc14 is essential to fulfil recombinational DNA repair in budding yeast. After DNA double‐strand break (DSB) generation, Cdc14 is transiently released from the nucleolus and activated. In this state, Cdc14 targets the spindle pole body (SPB) component Spc110 to counterbalance its phosphorylation by cyclin‐dependent kinase (Cdk). Alterations in the Cdk/Cdc14‐dependent phosphorylation status of Spc110, or its inactivation during the induction of a DNA lesion, generate abnormal oscillatory SPB movements that disrupt DSB‐SPB interactions. Remarkably, these defects impair DNA repair by homologous recombination indicating that SPB integrity is essential during the repair process. Together, these results show that Cdc14 promotes spindle stability and DSB‐SPB tethering during DNA repair, and imply that metaphase spindle maintenance is a critical feature of the repair process. John Wiley and Sons Inc. 2016-11-16 2017-01-04 /pmc/articles/PMC5210157/ /pubmed/27852625 http://dx.doi.org/10.15252/embj.201593540 Text en © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Villoria, María Teresa
Ramos, Facundo
Dueñas, Encarnación
Faull, Peter
Cutillas, Pedro Rodríguez
Clemente‐Blanco, Andrés
Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair
title Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair
title_full Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair
title_fullStr Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair
title_full_unstemmed Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair
title_short Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair
title_sort stabilization of the metaphase spindle by cdc14 is required for recombinational dna repair
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210157/
https://www.ncbi.nlm.nih.gov/pubmed/27852625
http://dx.doi.org/10.15252/embj.201593540
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