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

Autores
Capella, Matias; Mandemaker, Imke K.; Martín Caballero, Lucía; den Brave, Fabian; Pfander, Boris; Ladurner, Andreas G.; Jentsch, Stefan; Braun, Sigurd
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Capella, Matias. Max Planck Institute Of Biochemistry.; Alemania. Ludwig Maximilians Universitat; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mandemaker, Imke K.. Ludwig Maximilians Universitat; Alemania
Fil: Martín Caballero, Lucía. Ludwig Maximilians Universitat; Alemania. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania
Fil: den Brave, Fabian. Max-planck-institut Für Biochemie; Alemania. Universitat Bonn; Alemania
Fil: Pfander, Boris. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania. Max-planck-institut Für Biochemie; Alemania
Fil: Ladurner, Andreas G.. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania. Ludwig Maximilians Universitat; Alemania
Fil: Jentsch, Stefan. Max-planck-institut Für Biochemie; Alemania
Fil: Braun, Sigurd. Ludwig Maximilians Universitat; Alemania. Justus-liebig-universität Giessen; Alemania. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania
Materia
Ribosomal DNA
Genome stability
DNA damage
Saccharomyces cerevisiae
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/183992
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/183992
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregaseCapella, MatiasMandemaker, Imke K.Martín Caballero, Lucíaden Brave, FabianPfander, BorisLadurner, Andreas G.Jentsch, StefanBraun, SigurdRibosomal DNAGenome stabilityDNA damageSaccharomyces cerevisiaehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Ribosomal 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.Fil: Capella, Matias. Max Planck Institute Of Biochemistry.; Alemania. Ludwig Maximilians Universitat; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mandemaker, Imke K.. Ludwig Maximilians Universitat; AlemaniaFil: Martín Caballero, Lucía. Ludwig Maximilians Universitat; Alemania. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; AlemaniaFil: den Brave, Fabian. Max-planck-institut Für Biochemie; Alemania. Universitat Bonn; AlemaniaFil: Pfander, Boris. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania. Max-planck-institut Für Biochemie; AlemaniaFil: Ladurner, Andreas G.. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania. Ludwig Maximilians Universitat; AlemaniaFil: Jentsch, Stefan. Max-planck-institut Für Biochemie; AlemaniaFil: Braun, Sigurd. Ludwig Maximilians Universitat; Alemania. Justus-liebig-universität Giessen; Alemania. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; AlemaniaNature Publishing Group2021-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/183992Capella, Matias; Mandemaker, Imke K.; Martín Caballero, Lucía; den Brave, Fabian; Pfander, Boris; et al.; Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase; Nature Publishing Group; Nature Communications; 12; 1; 8-2021; 1-162041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-021-25205-2info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-25205-2info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:01:36Zoai:ri.conicet.gov.ar:11336/183992instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:01:37.019CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
title Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
spellingShingle Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
Capella, Matias
Ribosomal DNA
Genome stability
DNA damage
Saccharomyces cerevisiae
title_short Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
title_full Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
title_fullStr Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
title_full_unstemmed Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
title_sort Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
dc.creator.none.fl_str_mv Capella, Matias
Mandemaker, Imke K.
Martín Caballero, Lucía
den Brave, Fabian
Pfander, Boris
Ladurner, Andreas G.
Jentsch, Stefan
Braun, Sigurd
author Capella, Matias
author_facet Capella, Matias
Mandemaker, Imke K.
Martín Caballero, Lucía
den Brave, Fabian
Pfander, Boris
Ladurner, Andreas G.
Jentsch, Stefan
Braun, Sigurd
author_role author
author2 Mandemaker, Imke K.
Martín Caballero, Lucía
den Brave, Fabian
Pfander, Boris
Ladurner, Andreas G.
Jentsch, Stefan
Braun, Sigurd
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ribosomal DNA
Genome stability
DNA damage
Saccharomyces cerevisiae
topic Ribosomal DNA
Genome stability
DNA damage
Saccharomyces cerevisiae
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Capella, Matias. Max Planck Institute Of Biochemistry.; Alemania. Ludwig Maximilians Universitat; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mandemaker, Imke K.. Ludwig Maximilians Universitat; Alemania
Fil: Martín Caballero, Lucía. Ludwig Maximilians Universitat; Alemania. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania
Fil: den Brave, Fabian. Max-planck-institut Für Biochemie; Alemania. Universitat Bonn; Alemania
Fil: Pfander, Boris. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania. Max-planck-institut Für Biochemie; Alemania
Fil: Ladurner, Andreas G.. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania. Ludwig Maximilians Universitat; Alemania
Fil: Jentsch, Stefan. Max-planck-institut Für Biochemie; Alemania
Fil: Braun, Sigurd. Ludwig Maximilians Universitat; Alemania. Justus-liebig-universität Giessen; Alemania. International Max Planck Research School For Molecular Life Sciences: From Biological Structures To Neural Circuits; Alemania
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/183992
Capella, Matias; Mandemaker, Imke K.; Martín Caballero, Lucía; den Brave, Fabian; Pfander, Boris; et al.; Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase; Nature Publishing Group; Nature Communications; 12; 1; 8-2021; 1-16
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/183992
identifier_str_mv Capella, Matias; Mandemaker, Imke K.; Martín Caballero, Lucía; den Brave, Fabian; Pfander, Boris; et al.; Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase; Nature Publishing Group; Nature Communications; 12; 1; 8-2021; 1-16
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-021-25205-2
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-25205-2
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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