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

Matías Capella (), Imke K. Mandemaker, Lucía Martín Caballero, Fabian den Brave, Boris Pfander, Andreas G. Ladurner, Stefan Jentsch and Sigurd Braun ()
Additional contact information
Matías Capella: BioMedical Center (BMC), Ludwig-Maximillians-Universität München
Imke K. Mandemaker: BioMedical Center (BMC), Ludwig-Maximillians-Universität München
Lucía Martín Caballero: BioMedical Center (BMC), Ludwig-Maximillians-Universität München
Fabian den Brave: Max Planck Institute of Biochemistry, Molecular Cell Biology
Boris Pfander: International Max Planck Research School for Molecular and Cellular Life Sciences
Andreas G. Ladurner: BioMedical Center (BMC), Ludwig-Maximillians-Universität München
Stefan Jentsch: Max Planck Institute of Biochemistry, Molecular Cell Biology
Sigurd Braun: BioMedical Center (BMC), Ludwig-Maximillians-Universität München

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25205-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25205-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25205-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().