PT  - JOURNAL ARTICLE
AU  - Sandrine Morlot
AU  - Song Jia
AU  - Isabelle Léger-Silvestre
AU  - Audrey Matifas
AU  - Olivier Gadal
AU  - Gilles Charvin
TI  - Nucleolar stress causes the entry into replicative senescence in budding yeast
AID  - 10.1101/297093
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 297093
4099  - http://biorxiv.org/content/early/2018/06/07/297093.short
4100  - http://biorxiv.org/content/early/2018/06/07/297093.full
AB  - The accumulation of Extrachromosomal rDNA Circles (ERCs) and their asymmetric segregation upon division have been hypothesized to be responsible for replicative senescence in mother yeasts and rejuvenation in daughter cells. However, it remains unclear by which molecular mechanisms ERCs would trigger the irreversible cell cycle slow-down leading to cell death. We show that ERCs accumulation is concomitant with a nucleolar stress, characterized by a massive accumulation of pre-rRNAs in the nucleolus, leading to a loss of nucleus-to-cytoplasm ratio, decreased growth rate and cell-cycle slow-down. This nucleolar stress, observed in old mothers, is not inherited by rejuvenated daughters. Unlike WT, in the long-lived mutant fob1∆, a majority of cells is devoid of nucleolar stress and does not experience replicative senescence before death. Our study provides a unique framework to order the successive steps that govern the transition to replicative senescence and highlights the causal role of nucleolar stress in cellular aging.