The asymmetry of telomere replication contributes to replicative senescence heterogeneity.

ABSTRACT: 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 r

SUBMITTER: Bourgeron T 

PROVIDER: S-EPMC4606794 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature