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- Title
A two-step model for senescence triggered by a single critically short telomere.
- Authors
Abdallah, Pauline; Luciano, Pierre; Runge, Kurt W; Lisby, Michael; Géli, Vincent; Gilson, Eric; Teixeira, M Teresa
- 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.
- Publication
Nature cell biology, 2009, Vol 11, Issue 8, p988
- ISSN
1476-4679
- Publication type
Journal Article
- DOI
10.1038/ncb1911