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The asymmetry of telomere replication contributes to replicative senescence heterogeneity.

TitleThe asymmetry of telomere replication contributes to replicative senescence heterogeneity.
Publication TypeJournal Article
Year of Publication2015
AuthorsBourgeron, T, Xu, Z, Doumic, M, Teixeira, MTeresa
JournalSci Rep
Date Published2015 Oct 15
KeywordsCellular Senescence, DNA, Fungal, Models, Theoretical, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomere, Telomere Shortening

In eukaryotes, the absence of telomerase results in telomere shortening, eventually leading to replicative senescence, an arrested state that prevents further cell divisions. While replicative senescence is mainly controlled by telomere length, the heterogeneity of its onset is not well understood. This study proposes a mathematical model based on the molecular mechanisms of telomere replication and shortening to decipher the causes of this heterogeneity. Using simulations fitted on experimental data obtained from individual lineages of senescent Saccharomyces cerevisiae cells, we decompose the sources of senescence heterogeneity into interclonal and intraclonal components, and show that the latter is based on the asymmetry of the telomere replication mechanism. We also evidence telomere rank-switching events with distinct frequencies in short-lived versus long-lived lineages, revealing that telomere shortening dynamics display important variations. Thus, the intrinsic heterogeneity of replicative senescence and its consequences find their roots in the asymmetric structure of telomeres.

Alternate JournalSci Rep
PubMed ID26468778
PubMed Central IDPMC4606794
Grant List260906 / / European Research Council / International

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