DNA circles promote yeast ageing in part through stimulating the reorganization of nuclear pore complexes

  1. Anne C Meinema
  2. Anna Marzelliusardottir
  3. Mihailo Mirkovic
  4. Théo Aspert
  5. Sung Sik Lee
  6. Gilles Charvin
  7. Yves Barral  Is a corresponding author
  1. ETH Zürich, Switzerland
  2. Institute of Genetics and Molecular and Cellular Biology, France

Abstract

The nuclear pore complex (NPC) mediates nearly all exchanges between nucleus and cytoplasm, and in many species it changes composition as the organism ages. However, how these changes arise and whether they contribute themselves to ageing is poorly understood. We show that SAGA-dependent attachment of DNA circles to NPCs in replicatively ageing yeast cells causes NPCs to lose their nuclear basket and cytoplasmic complexes. These NPCs were not recognized as defective by the NPC quality control machinery (SINC) and not targeted by ESCRTs. They interacted normally or more effectively with protein import and export factors but specifically lost mRNA export factors. Acetylation of Nup60 drove the displacement of basket and cytoplasmic complexes from circle-bound NPCs. Mutations preventing this remodeling extended the replicative lifespan of the cells. Thus, our data suggest that the anchorage of accumulating circles locks NPCs in a specialized state and that this process is intrinsically linked to the mechanisms by which ERCs promote ageing.

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All data generated or analysed during this study are included in the manuscript and supporting files

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Author details

  1. Anne C Meinema

    Department of Biology, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0002-3486
  2. Anna Marzelliusardottir

    Department of Biology, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Mihailo Mirkovic

    Department of Biology, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Théo Aspert

    Department of Developmental Biology and Stem Cells, Institute of Genetics and Molecular and Cellular Biology, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2957-0683
  5. Sung Sik Lee

    Department of Biology, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9267-232X
  6. Gilles Charvin

    Department of Developmental Biology and Stem Cells, Institute of Genetics and Molecular and Cellular Biology, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6852-6952
  7. Yves Barral

    Department of Biology, ETH Zürich, Zürich, Switzerland
    For correspondence
    yves.barral@bc.biol.ethz.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0989-3373

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A-105904)

  • Yves Barral

H2020 European Research Council (899417)

  • Yves Barral

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Meinema et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Anne C Meinema
  2. Anna Marzelliusardottir
  3. Mihailo Mirkovic
  4. Théo Aspert
  5. Sung Sik Lee
  6. Gilles Charvin
  7. Yves Barral
(2022)
DNA circles promote yeast ageing in part through stimulating the reorganization of nuclear pore complexes
eLife 11:e71196.
https://doi.org/10.7554/eLife.71196

Share this article

https://doi.org/10.7554/eLife.71196

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