Adaptation in replicative senescence: a risky business
Cell proliferation is tightly regulated to avoid propagating DNA damage and mutations, which can lead to pathologies such as cancer. To ensure genome integrity, cells activate the DNA damage checkpoint in response to genotoxic lesions to block cell cycle progression. This surveillance mechanism provides time to repair the damage before resuming cell cycle with an intact genome. When the damage is not repaired, cells can, in some conditions, override the cell cycle arrest and proceed with proliferation, a phenomenon known as adaptation to DNA damage. A subpopulation of adapted cells might eventually survive, but only at the cost of extensive genome instability. How and in which context adaptation operates the trade-off between survival and genome stability is a fascinating question. After a brief review of the current knowledge on adaptation to DNA damage in budding yeast, we will discuss a new role of adaptation in the context of telomerase-negative cells and replicative senescence. We highlight the idea that, in all settings studied so far, survival through adaptation is a double-edged sword as it comes with increased genomic instability.
KeywordsAdaptation to DNA damage Telomere Repair Genome instability Polo kinase
We thank Maria Teresa Teixeira and Karine Dubrana for their critical reading of the manuscript. This work was supported by “Fondation pour la Recherche Médicale” (“équipe labellisée”) and the French National Research Agency (ANR) grant ANR-16-CE12-0026 to Maria Teresa Teixeira in whose lab the work was done, and ANR grant ANR-17-CE20-0002-01 to ZX. HC has been supported by a doctoral grant from the Paris Sciences et Lettres (PSL) Idex program implemented by the ANR (ANR-10-IDEX-0001-02 PSL).
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Conflict of interest
The authors declare that they have no conflict of interest.
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