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Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation

Author

Listed:
  • Clémence Mooser

    (University of Zurich)

  • Ioanna-Eleni Symeonidou

    (University of Zurich)

  • Pia-Amata Leimbacher

    (University of Zurich)

  • Alison Ribeiro

    (University of Zurich)

  • Ann-Marie K. Shorrocks

    (University of Oxford, John Radcliffe Hospital
    University of Oxford)

  • Stephanie Jungmichel

    (University of Copenhagen, Faculty of Health and Medical Sciences)

  • Sara C. Larsen

    (University of Copenhagen, Faculty of Health and Medical Sciences)

  • Katja Knechtle

    (University of Zurich)

  • Arti Jasrotia

    (University of Zurich)

  • Diana Zurbriggen

    (University of Zurich)

  • Alain Jeanrenaud

    (University of Zurich)

  • Colin Leikauf

    (University of Zurich)

  • Daniel Fink

    (University of Zurich)

  • Michael L. Nielsen

    (University of Copenhagen, Faculty of Health and Medical Sciences)

  • Andrew N. Blackford

    (University of Oxford, John Radcliffe Hospital
    University of Oxford)

  • Manuel Stucki

    (University of Zurich)

Abstract

Induction of DNA double-strand breaks (DSBs) in ribosomal DNA (rDNA) repeats is associated with ATM-dependent repression of ribosomal RNA synthesis and large-scale reorganization of nucleolar architecture, but the signaling events that regulate these responses are largely elusive. Here we show that the nucleolar response to rDNA breaks is dependent on both ATM and ATR activity. We further demonstrate that ATM- and NBS1-dependent recruitment of TOPBP1 in the nucleoli is required for inhibition of ribosomal RNA synthesis and nucleolar segregation in response to rDNA breaks. Mechanistically, TOPBP1 recruitment is mediated by phosphorylation-dependent interactions between three of its BRCT domains and conserved phosphorylated Ser/Thr residues at the C-terminus of the nucleolar phosphoprotein Treacle. Our data thus reveal an important cooperation between TOPBP1 and Treacle in the signaling cascade that triggers transcriptional inhibition and nucleolar segregation in response to rDNA breaks.

Suggested Citation

  • Clémence Mooser & Ioanna-Eleni Symeonidou & Pia-Amata Leimbacher & Alison Ribeiro & Ann-Marie K. Shorrocks & Stephanie Jungmichel & Sara C. Larsen & Katja Knechtle & Arti Jasrotia & Diana Zurbriggen &, 2020. "Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13981-x
    DOI: 10.1038/s41467-019-13981-x
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    Cited by:

    1. Zita Gál & Stavroula Boukoura & Kezia Catharina Oxe & Sara Badawi & Blanca Nieto & Lea Milling Korsholm & Sille Blangstrup Geisler & Ekaterina Dulina & Anna Vestergaard Rasmussen & Christina Dahl & We, 2024. "Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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