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Cdc14 phosphatase counteracts Cdk-dependent Dna2 phosphorylation to inhibit resection during recombinational DNA repair

Author

Listed:
  • Adrián Campos

    (Instituto de Biología Funcional y Genómica (IBFG), CSIC-USAL)

  • Facundo Ramos

    (Instituto de Biología Funcional y Genómica (IBFG), CSIC-USAL)

  • Lydia Iglesias

    (Instituto de Biología Funcional y Genómica (IBFG), CSIC-USAL)

  • Celia Delgado

    (Instituto de Biología Funcional y Genómica (IBFG), CSIC-USAL)

  • Eva Merino

    (Instituto de Biología Funcional y Genómica (IBFG), CSIC-USAL)

  • Antonio Esperilla-Muñoz

    (Universidad de Extremadura)

  • Jaime Correa-Bordes

    (Universidad de Extremadura)

  • Andrés Clemente-Blanco

    (Instituto de Biología Funcional y Genómica (IBFG), CSIC-USAL)

Abstract

Cyclin-dependent kinase (Cdk) stimulates resection of DNA double-strand breaks ends to generate single-stranded DNA (ssDNA) needed for recombinational DNA repair. Here we show in Saccharomyces cerevisiae that lack of the Cdk-counteracting phosphatase Cdc14 produces abnormally extended resected tracts at the DNA break ends, involving the phosphatase in the inhibition of resection. Over-resection in the absence of Cdc14 activity is bypassed when the exonuclease Dna2 is inactivated or when its Cdk consensus sites are mutated, indicating that the phosphatase restrains resection by acting through this nuclease. Accordingly, mitotically activated Cdc14 promotes Dna2 dephosphorylation to exclude it from the DNA lesion. Cdc14-dependent resection inhibition is essential to sustain DNA re-synthesis, thus ensuring the appropriate length, frequency, and distribution of the gene conversion tracts. These results establish a role for Cdc14 in controlling the extent of resection through Dna2 regulation and demonstrate that the accumulation of excessively long ssDNA affects the accurate repair of the broken DNA by homologous recombination.

Suggested Citation

  • Adrián Campos & Facundo Ramos & Lydia Iglesias & Celia Delgado & Eva Merino & Antonio Esperilla-Muñoz & Jaime Correa-Bordes & Andrés Clemente-Blanco, 2023. "Cdc14 phosphatase counteracts Cdk-dependent Dna2 phosphorylation to inhibit resection during recombinational DNA repair," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38417-5
    DOI: 10.1038/s41467-023-38417-5
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    References listed on IDEAS

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