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"Adaptive mutations" in the S/MAPK pathways provide selective advantage in quiescent fission yeast

Abstract : Quiescence and proliferation reflect two fundamentally different cellular stages, yet very limited information exists on how cells maintain their genome stability in quiescence. Using nitrogen-starved fission yeast as a model for quiescence, our laboratory has demonstrated that cells are not only subject to DNA damage in G0 but also accumulate replication-independent mutations linearly with time. In our current work, we have demonstrated that mutations accumulating in growth-arrested phase undergo a selection process in quiescence similar to that observed in E. coli. Selection favors mutations that affect functions of the genes of the MAP-kinase (mkh1, pek1, pmk1) and SAP-kinase pathways (win1, wis1, sty1), and their downstream targets (pmc1, sgf73, tif452). These genes represent core cellular signaling that regulates cell proliferation, cell differentiation, and cell death conserved among all eukaryotic species from yeast to human. Mutations in components of the S/MAPK pathways and their regulators are associated with multiple diseases in humans, primary cancer and degenerative neuronal death accumulated with ageing. In this work, we have demonstrated that wild-type cells dying in quiescence release traces of nitrogen that triggers the viable population to exit from quiescence. The wild-type cells are dying during their entry into S-phase releasing more nitrogen. Thus, mutants in the S/MAPK pathways are better scavengers and selection in quiescence is characterized by the ability of the mutant to resume cycling in quiescence coupled with a resistance to programed cell death.
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Submitted on : Friday, February 12, 2021 - 5:11:10 PM
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  • HAL Id : tel-03140324, version 1

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Rostyslav Makarenko. "Adaptive mutations" in the S/MAPK pathways provide selective advantage in quiescent fission yeast. Cellular Biology. Sorbonne Université, 2019. English. ⟨NNT : 2019SORUS253⟩. ⟨tel-03140324⟩

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