IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38417-5.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38417-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38417-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Pablo Huertas & Felipe Cortés-Ledesma & Alessandro A. Sartori & Andrés Aguilera & Stephen P. Jackson, 2008. "CDK targets Sae2 to control DNA-end resection and homologous recombination," Nature, Nature, vol. 455(7213), pages 689-692, October.
    2. Grzegorz Ira & Achille Pellicioli & Alitukiriza Balijja & Xuan Wang & Simona Fiorani & Walter Carotenuto & Giordano Liberi & Debra Bressan & Lihong Wan & Nancy M. Hollingsworth & James E. Haber & Marc, 2004. "DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1," Nature, Nature, vol. 431(7011), pages 1011-1017, October.
    3. Eleni P. Mimitou & Lorraine S. Symington, 2008. "Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing," Nature, Nature, vol. 455(7214), pages 770-774, October.
    4. Nozomi Tomimatsu & Bipasha Mukherjee & Molly Catherine Hardebeck & Mariya Ilcheva & Cristel Vanessa Camacho & Janelle Louise Harris & Matthew Porteus & Bertrand Llorente & Kum Kum Khanna & Sandeep Bur, 2014. "Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    5. Andrés Clemente-Blanco & María Mayán-Santos & David A. Schneider & Félix Machín & Adam Jarmuz & Herbert Tschochner & Luis Aragón, 2009. "Cdc14 inhibits transcription by RNA polymerase I during anaphase," Nature, Nature, vol. 458(7235), pages 219-222, March.
    6. Jessel Ayra-Plasencia & Félix Machín, 2019. "DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    7. Jessel Ayra-Plasencia & Félix Machín, 2019. "Publisher Correction: DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci," Nature Communications, Nature, vol. 10(1), pages 1-1, December.
    8. Rosella Visintin & Ellen S. Hwang & Angelika Amon, 1999. "Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus," Nature, Nature, vol. 398(6730), pages 818-823, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Lorenzo Galanti & Martina Peritore & Robert Gnügge & Elda Cannavo & Johannes Heipke & Maria Dilia Palumbieri & Barbara Steigenberger & Lorraine S. Symington & Petr Cejka & Boris Pfander, 2024. "Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Vera M. Kissling & Giordano Reginato & Eliana Bianco & Kristina Kasaciunaite & Janny Tilma & Gea Cereghetti & Natalie Schindler & Sung Sik Lee & Raphaël Guérois & Brian Luke & Ralf Seidel & Petr Cejka, 2022. "Mre11-Rad50 oligomerization promotes DNA double-strand break repair," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    4. Qian Zhu & Jinzhou Huang & Hongyang Huang & Huan Li & Peiqiang Yi & Jake A. Kloeber & Jian Yuan & Yuping Chen & Min Deng & Kuntian Luo & Ming Gao & Guijie Guo & Xinyi Tu & Ping Yin & Yong Zhang & Jun , 2021. "RNF19A-mediated ubiquitination of BARD1 prevents BRCA1/BARD1-dependent homologous recombination," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. Erica J. Polleys & Isabella Priore & James E. Haber & Catherine H. Freudenreich, 2023. "Structure-forming CAG/CTG repeats interfere with gap repair to cause repeat expansions and chromosome breaks," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Ashish Kumar Singh & Tamás Schauer & Lena Pfaller & Tobias Straub & Felix Mueller-Planitz, 2021. "The biogenesis and function of nucleosome arrays," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    7. Priya Kapoor-Vazirani & Sandip K. Rath & Xu Liu & Zhen Shu & Nicole E. Bowen & Yitong Chen & Ramona Haji-Seyed-Javadi & Waaqo Daddacha & Elizabeth V. Minten & Diana Danelia & Daniela Farchi & Duc M. D, 2022. "SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    8. Bert Kooij & Fenna J. Wal & Magdalena B. Rother & Wouter W. Wiegant & Pau Creixell & Merula Stout & Brian A. Joughin & Julia Vornberger & Matthias Altmeyer & Marcel A. T. M. Vugt & Michael B. Yaffe & , 2024. "The Fanconi anemia core complex promotes CtIP-dependent end resection to drive homologous recombination at DNA double-strand breaks," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38417-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.