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Adaptation in replicative senescence: a risky business.

TitleAdaptation in replicative senescence: a risky business.
Publication TypeJournal Article
Year of Publication2019
AuthorsCoutelier, H, Xu, Z
JournalCurr Genet
Date Published2019 Jan 12
ISSN1432-0983
Abstract

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.

DOI10.1007/s00294-019-00933-7
Alternate JournalCurr. Genet.
PubMed ID30637477
Grant ListANR-16-CE12-0026 / / Agence Nationale de la Recherche /
ANR-17-CE20-0002-01 / / Agence Nationale de la Recherche /
ANR-10-IDEX-0001-02 PSL / / Agence Nationale de la Recherche /
- / / Fondation pour la recherche m?dicale /