The length of the shortest telomere as the major determinant of the onset of replicative senescence.

ABSTRACT: The absence of telomerase in many eukaryotes leads to the gradual shortening of telomeres, causing replicative senescence. In humans, this proliferation barrier constitutes a tumor suppressor mechanism and may be involved in cellular aging. Yet the heterogeneity of the senescence phenotype has hindered the understanding of its onset. Here we investigated the regulation of telomere length and its control of senescence heterogeneity. Because the length of the shortest telomeres can potentially regulate cell fate, we focus on their dynamics in Saccharomyces cerevisiae. We developed a stochastic model of telomere dynamics built on the protein-counting model, where an increasing number of protein-bound telomeric repeats shift telomeres into a nonextendable state by telomerase. Using numerical s

SUBMITTER: Xu Z 

PROVIDER: S-EPMC3730915 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature