RT Journal Article
SR Electronic
T1 Nucleolar stress causes the entry into replicative senescence in budding yeast
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 297093
DO 10.1101/297093
A1 Sandrine Morlot
A1 Song Jia
A1 Isabelle Léger-Silvestre
A1 Audrey Matifas
A1 Olivier Gadal
A1 Gilles Charvin
YR 2018
UL http://biorxiv.org/content/early/2018/06/07/297093.abstract
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.