A two-step model for senescence triggered by a single critically short telomere
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A two-step model for senescence triggered by a single critically short telomere. / Abdallah, Pauline; Luciano, Pierre; Runge, Kurt W; Lisby, Michael; Géli, Vincent; Gilson, Eric; Teixeira, M Teresa.
I: Nature Cell Biology, Bind 11, Nr. 8, 2009, s. 988-93.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A two-step model for senescence triggered by a single critically short telomere
AU - Abdallah, Pauline
AU - Luciano, Pierre
AU - Runge, Kurt W
AU - Lisby, Michael
AU - Géli, Vincent
AU - Gilson, Eric
AU - Teixeira, M Teresa
N1 - 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
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1038/ncb1911
DO - 10.1038/ncb1911
M3 - Journal article
C2 - 19597486
VL - 11
SP - 988
EP - 993
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 8
ER -
ID: 16586126