DNA circles promote yeast ageing in part through stimulating the reorganization of nuclear pore complexes.
Fiche publication
Date publication
avril 2022
Journal
eLife
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHARVIN Gilles
Tous les auteurs :
Meinema AC, Marzelliusardottir A, Mirkovic M, Aspert T, Lee SS, Charvin G, Barral Y
Lien Pubmed
Résumé
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.
Mots clés
S. cerevisiae, cell biology, evolutionary biology
Référence
Elife. 2022 Apr 4;11: