Biology subjects

Matifas, A.

Publications and source records attributed to Matifas, A..

4 recordsLinked to original sources

bioRxiv2021

A trade-off between stress resistance and tolerance underlies the adaptive response to hydrogen peroxide

The physiological adaptation to environmental stress involves complex molecular responses leading to separate cellular fates aimed at maximizing fitness: either cells can maintain proliferation by degrading the effects of the stressor (i.e. resistance), or they focus on ensuring cell survival (i.e. tolerance), even at the expense of proliferation. These strategies are complementary, yet whether they are coordinated to ensure an optimal physiological stress response remains unknown. Here, we used microfluidics and live cell imaging to explore the genetic basis of the interplay between resistance and tolerance during the response to hydrogen peroxide (H2O2) in budding yeast. Our analysis unraveled that the deletion of zwf1{Delta}, which is responsible for NADPH synthesis via the PPP pathway, led to a decrease in resistance that was counterbalanced by an unexpected exacerbation of tolerance to H2O2. This trade-off between stress resistance and stress tolerance was further characterized using both genetic and environmental interventions, and we confirmed that it was conserved in bacteria. Our results support a model in which redox signaling triggers the switch to a nutrients-dependent non-proliferative tolerant state via inhibition of protein kinase A when the H2O2 homeostatic response is overwhelmed. Our framework could help develop synergistic therapies that target mechanisms driving both resistance and tolerance to prevent drug escape mechanisms and disease relapse.

cell biology↗

bioRxiv2019

COSPLAY: An expandable toolbox for combinatorial and swift generation of expression plasmids in yeast

A large number of genetic studies in yeast rely on the use of expression vectors. To facilitate the experimental approach of these studies, several collections of expression vectors have been generated (YXplac, pRS series, etc.). Subsequently, these collections have been expanded by adding more diversity to many of the plasmid features, including new selection markers and new promoter sequences. However, the ever growing number of plasmid feature makes it unrealistic for research labs to maintain an up-to-date collection of plasmids.. Here, we developed the COSPLAY toolbox: a Golden Gate approach based on the scheme of a simple modular plasmid that recapitulates and completes all the properties of the pRS plasmids. The COSPLAY toolbox contains a basal collection of individual functional modules. Moreover we standardized a simple and rapid, software-assisted protocol which facilitates the addition of new personalized modules. Finally, our toolbox includes the possibility to select a genomic target location and to perform a single copy integration of the expression vector.

molecular biology↗

bioRxiv2018

Nucleolar stress triggers the irreversible cell cycle slow down leading to cell death during replicative aging in Saccharomyces cerevisiae

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{triangleup}, 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.

cell biology↗

bioRxiv2017

Multiple inputs ensure yeast cell size homeostasis during cell cycle progression

Coordination of cell growth and division is essential for proper cell function. In budding yeast, although some molecular mechanisms responsible for cell size control during G1 have been elucidated, the mechanism by which cell size homeostasis is established and maintained throughout the cell cycle remains to be discovered. Here, we developed a new technique based on quantification of histone levels to monitor cell cycle progression in individual yeast cells with unprecedented accuracy. Our analysis establishes the existence of a strong mechanism controlling bud size in G2/M that prevents premature entry into mitosis, and contributes significantly to the overall control of size variability during the cell cycle. While most G1/S regulation mutants do not display any strongly impaired size homeostasis, mutants in which B-type cyclin regulation is altered display large cell-to-cell size variability. Our study thus demonstrates that size homeostasis is not controlled by a G1-specific mechanism but is likely to be an emergent property resulting from the integration of several mechanisms, including the control of cyclin B-Cdk activity, that coordinate cell and bud growth with division.

cell biology↗