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

• María Teresa Villoria ^[2] ; Facundo Ramos ^[2] ; Encarnación Dueñas ^[2] ; Peter Faull ^[1] ; Pedro Rodríguez Cutillas ^[3] ; Andrés Clemente‐Blanco ^[2]
  1. [1] Imperial College London

     Imperial College London

     Reino Unido

     
  2. [2] 1 Cell Cycle and Genome Stability Group Instituto de Biología Funcional y Genómica Consejo Superior de Investigaciones Científicas (CSIC) Universidad de Salamanca (USAL) Salamanca Spain
  3. [3] 2 Biological Mass Spectrometry and Proteomics Laboratory Medical Research Council Clinical Science Centre Imperial College London UK; Present address: Integrative Cell Signalling and Proteomics GroupCentre for Haemato‐OncologyBarts Cancer InstituteJohn Vane Science CentreQueen Mary University of LondonLondonUK

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 1, 2017, págs. 79-101
• Idioma: inglés
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  • 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.