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

María Teresa Villoria1, Facundo Ramos1, Encarnación Dueñas1

  • 1Cell Cycle and Genome Stability Group, Instituto de Biología Funcional y Genómica Consejo Superior de Investigaciones Científicas (CSIC) Universidad de Salamanca (USAL), Salamanca, Spain.

The EMBO Journal
|November 18, 2016
PubMed

Insights

The phosphatase Cdc14 is crucial for DNA repair by maintaining spindle stability and tethering DNA breaks. This study reveals Cdc14

Area of Science:

  • Cellular biology
  • Molecular genetics
  • Biochemistry

Background:

  • Cells face constant DNA damage from genotoxic stress.
  • The DNA damage response (DDR) network maintains genome integrity.
  • The role of protein dephosphorylation in DDR is not well understood.

Purpose of the Study:

  • Investigate the role of phosphatase Cdc14 in DNA repair.
  • Elucidate the mechanism by which Cdc14 participates in the DNA damage response.
  • Determine the importance of spindle pole body (SPB) integrity during DNA repair.

Main Methods:

  • Utilized budding yeast as a model organism.
  • Induced DNA double-strand breaks (DSBs) to trigger DNA damage response.
  • Analyzed the activity and localization of Cdc14 phosphatase.
  • Assessed the phosphorylation status of Spc110 by cyclin-dependent kinase (Cdk).
  • Observed SPB movements and DSB-SPB interactions.

Main Results:

  • Cdc14 is essential for recombinational DNA repair.
  • Cdc14 is released from the nucleolus and activated upon DSB generation.
  • Cdc14 dephosphorylates Spc110, counterbalancing Cdk phosphorylation.
  • Altered Spc110 phosphorylation leads to abnormal SPB oscillations and disrupts DSB-SPB interactions.
  • These defects impair homologous recombination repair.

Conclusions:

  • Cdc14 promotes spindle stability and DSB-SPB tethering during DNA repair.
  • SPB integrity is critical for efficient homologous recombination.
  • Metaphase spindle maintenance is a key feature of the DNA repair process.
Keywords:
Cdc14DNA repairdouble‐strand breakhomologous recombinationspindle pole body

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