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Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase

Author

Listed:
  • Matías Capella

    (BioMedical Center (BMC), Ludwig-Maximillians-Universität München
    Max Planck Institute of Biochemistry, Molecular Cell Biology)

  • Imke K. Mandemaker

    (BioMedical Center (BMC), Ludwig-Maximillians-Universität München)

  • Lucía Martín Caballero

    (BioMedical Center (BMC), Ludwig-Maximillians-Universität München
    International Max Planck Research School for Molecular and Cellular Life Sciences)

  • Fabian den Brave

    (Max Planck Institute of Biochemistry, Molecular Cell Biology
    University of Bonn)

  • Boris Pfander

    (International Max Planck Research School for Molecular and Cellular Life Sciences
    Max Planck Institute of Biochemistry, DNA Replication and Genome Integrity)

  • Andreas G. Ladurner

    (BioMedical Center (BMC), Ludwig-Maximillians-Universität München
    International Max Planck Research School for Molecular and Cellular Life Sciences)

  • Stefan Jentsch

    (Max Planck Institute of Biochemistry, Molecular Cell Biology)

  • Sigurd Braun

    (BioMedical Center (BMC), Ludwig-Maximillians-Universität München
    International Max Planck Research School for Molecular and Cellular Life Sciences
    Institute for Genetics, Justus-Liebig University Giessen)

Abstract

Ribosomal RNA genes (rDNA) are highly unstable and susceptible to rearrangement due to their repetitive nature and active transcriptional status. Sequestration of rDNA in the nucleolus suppresses uncontrolled recombination. However, broken repeats must be first released to the nucleoplasm to allow repair by homologous recombination. Nucleolar release of broken rDNA repeats is conserved from yeast to humans, but the underlying molecular mechanisms are currently unknown. Here we show that DNA damage induces phosphorylation of the CLIP-cohibin complex, releasing membrane-tethered rDNA from the nucleolus in Saccharomyces cerevisiae. Downstream of phosphorylation, SUMOylation of CLIP-cohibin is recognized by Ufd1 via its SUMO-interacting motif, which targets the complex for disassembly through the Cdc48/p97 chaperone. Consistent with a conserved mechanism, UFD1L depletion in human cells impairs rDNA release. The dynamic and regulated assembly and disassembly of the rDNA-tethering complex is therefore a key determinant of nucleolar rDNA release and genome integrity.

Suggested Citation

  • Matías Capella & Imke K. Mandemaker & Lucía Martín Caballero & Fabian den Brave & Boris Pfander & Andreas G. Ladurner & Stefan Jentsch & Sigurd Braun, 2021. "Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25205-2
    DOI: 10.1038/s41467-021-25205-2
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