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Regulatory control of DNA end resection by Sae2 phosphorylation

Author

Listed:
  • Elda Cannavo

    (Università della Svizzera italiana (USI))

  • Dominic Johnson

    (University of Sussex)

  • Sara N. Andres

    (US National Institutes of Health
    McMaster University)

  • Vera M. Kissling

    (Eidgenössische Technische Hochschule (ETH))

  • Julia K. Reinert

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Valerie Garcia

    (University of Sussex
    Institut Paoli Calmettes, Inserm UMR1068, CNRS UMR7258, Aix Marseille Université)

  • Dorothy A. Erie

    (University of North Carolina)

  • Daniel Hess

    (Friedrich Miescher Institute for Biomedical Research)

  • Nicolas H. Thomä

    (Friedrich Miescher Institute for Biomedical Research)

  • Radoslav I. Enchev

    (Eidgenössische Technische Hochschule (ETH))

  • Matthias Peter

    (Eidgenössische Technische Hochschule (ETH))

  • R. Scott Williams

    (US National Institutes of Health)

  • Matt J. Neale

    (University of Sussex)

  • Petr Cejka

    (Università della Svizzera italiana (USI)
    Eidgenössische Technische Hochschule (ETH))

Abstract

DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to initiate resection of blocked DNA ends by at least two distinct mechanisms. First, DNA damage and cell cycle-dependent phosphorylation leads to Sae2 tetramerization. Second, and independently, phosphorylation of the conserved C-terminal domain of Sae2 is a prerequisite for its physical interaction with Rad50, which is also crucial to promote the MRX endonuclease. The lack of this interaction explains the phenotype of rad50S mutants defective in the processing of Spo11-bound DNA ends during meiotic recombination. Our results define how phosphorylation controls the initiation of DNA end resection and therefore the choice between the key DNA double-strand break repair mechanisms.

Suggested Citation

  • Elda Cannavo & Dominic Johnson & Sara N. Andres & Vera M. Kissling & Julia K. Reinert & Valerie Garcia & Dorothy A. Erie & Daniel Hess & Nicolas H. Thomä & Radoslav I. Enchev & Matthias Peter & R. Sco, 2018. "Regulatory control of DNA end resection by Sae2 phosphorylation," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06417-5
    DOI: 10.1038/s41467-018-06417-5
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    Cited by:

    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. Tomoki Tamai & Giordano Reginato & Ryusei Ojiri & Issei Morita & Alexandra Avrutis & Petr Cejka & Miki Shinohara & Katsunori Sugimoto, 2024. "Sae2 controls Mre11 endo- and exonuclease activities by different mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. 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.

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