title: Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair.
abstract: 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.
authors.affiliation: Cell Cycle and Genome Stability Group, Instituto de Biología Funcional y Genómica Consejo Superior de Investigaciones Científicas (CSIC) Universidad de Salamanca (USAL), Salamanca, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Villoria
authors.affiliation: Cell Cycle and Genome Stability Group, Instituto de Biología Funcional y Genómica Consejo Superior de Investigaciones Científicas (CSIC) Universidad de Salamanca (USAL), Salamanca, Spain.
authors.forename: Facundo
authors.initials: F
authors.lastname: Ramos
authors.affiliation: Cell Cycle and Genome Stability Group, Instituto de Biología Funcional y Genómica Consejo Superior de Investigaciones Científicas (CSIC) Universidad de Salamanca (USAL), Salamanca, Spain.
authors.forename: Encarnación
authors.initials: E
authors.lastname: Dueñas
authors.affiliation: Biological Mass Spectrometry and Proteomics Laboratory, Medical Research Council Clinical Science Centre Imperial College, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Faull
authors.affiliation: Biological Mass Spectrometry and Proteomics Laboratory, Medical Research Council Clinical Science Centre Imperial College, London, UK.
authors.forename: Pedro Rodríguez
authors.initials: PR
authors.lastname: Cutillas
authors.affiliation: Cell Cycle and Genome Stability Group, Instituto de Biología Funcional y Genómica Consejo Superior de Investigaciones Científicas (CSIC) Universidad de Salamanca (USAL), Salamanca, Spain andresclemente@usal.es.
authors.forename: Andrés
authors.identifier: 0000-0002-3674-0671
authors.initials: A
authors.lastname: Clemente-Blanco
mesh_terms: D002148:Calmodulin-Binding Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D008677:Metaphase; D009687:Nuclear Proteins / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D059767:Recombinational DNA Repair; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C074860:CDC14 protein, S cerevisiae; D002148:Calmodulin-Binding Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C073277:SPC110 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018844:Cyclin-Dependent Kinases; D017027:Protein Tyrosine Phosphatases
keywords: Cdc14; DNA repair; double‐strand break; homologous recombination; spindle pole body