DNA circles promote yeast ageing in part through stimulating the reorganization of nuclear pore complexes
- ETH Zürich, Switzerland
- 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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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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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
