@article{07e5e7e0f3a311deba73000ea68e967b,
title = "A two-step model for senescence triggered by a single critically short telomere",
abstract = "Telomeres protect chromosome ends from fusion and degradation. In the absence of a specific telomere elongation mechanism, their DNA shortens progressively with every round of replication, leading to replicative senescence. Here, we show that telomerase-deficient cells bearing a single, very short telomere senesce earlier, demonstrating that the length of the shortest telomere is a major determinant of the onset of senescence. We further show that Mec1p-ATR specifically recognizes the single, very short telomere causing the accelerated senescence. Strikingly, before entering senescence, cells divide for several generations despite complete erosion of their shortened telomeres. This pre-senescence growth requires RAD52 (radiation sensitive) and MMS1 (methyl methane sulfonate sensitive), and there is no evidence for major inter-telomeric recombination. We propose that, in the absence of telomerase, a very short telomere is first maintained in a pre-signalling state by a RAD52-MMS1-dependent pathway and then switches to a signalling state leading to senescence through a Mec1p-dependent checkpoint.",
author = "Pauline Abdallah and Pierre Luciano and Runge, {Kurt W} and Michael Lisby and Vincent G{\'e}li and Eric Gilson and Teixeira, {M Teresa}",
note = "Keywords: Cell Cycle; Cell Division; DNA Nucleotidyltransferases; Intracellular Signaling Peptides and Proteins; Models, Biological; Mutation; Protein Binding; Protein-Serine-Threonine Kinases; Rad52 DNA Repair and Recombination Protein; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Spores, Fungal; Telomerase; Telomere",
year = "2009",
doi = "10.1038/ncb1911",
language = "English",
volume = "11",
pages = "988--93",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "nature publishing group",
number = "8",
}