Excessive rDNA Transcription Drives the Disruption in Nuclear Homeostasis during Entry into Senescence in Budding Yeast.
Fiche publication
Date publication
juillet 2019
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHARVIN Gilles
Tous les auteurs :
Morlot S, Song J, Léger-Silvestre I, Matifas A, Gadal O, Charvin G
Lien Pubmed
Résumé
Budding yeast cells undergo a limited number of divisions before they enter senescence and die. Despite recent mechanistic advances, whether and how molecular events are temporally and causally linked during the transition to senescence remain elusive. Here, using real-time observation of the accumulation of extrachromosomal rDNA circles (ERCs) in single cells, we provide evidence that ERCs build up rapidly with exponential kinetics well before any physiological decline. We then show that ERCs fuel a massive increase in ribosomal RNA (rRNA) levels in the nucleolus, which do not mature into functional ribosomes. This breakdown in nucleolar coordination is followed by a loss of nuclear homeostasis, thus defining a chronology of causally related events leading to cell death. A computational analysis supports a model in which a series of age-independent processes lead to an age-dependent increase in cell mortality, hence explaining the emergence of aging in budding yeast.
Mots clés
ERCs, live cell imaging, microfluidics, nucleolus, rDNA, ribosome biogenesis, yeast replicative aging
Référence
Cell Rep. 2019 07 9;28(2):408-422.e4