CHK2-independent induction of telomere dysfunction checkpoints in stem and progenitor cells

Telomere shortening limits the proliferation of primary human fibroblasts by the induction of senescence, which is mediated by ataxia telangiectasia mutated‐dependent activation of p53. Here, we show that CHK2 deletion impairs the induction of senescence in mouse and human fibroblasts. By contrast,...

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Bibliographic Details
Published in:EMBO reports 2010-08, Vol.11 (8), p.619-625
Main Authors: Nalapareddy, Kodandaramireddy, Choudhury, Aaheli Roy, Gompf, Anne, Ju, Zhenyu, Ravipati, Satyavani, Leucht, Thomas, Lechel, André, Rudolph, K Lenhard
Format: Article
Language:English
Subjects:
Animals
Binding sites
Cell Cycle - physiology
Cellular Senescence - physiology
Checkpoint Kinase 2
CHK2
DNA Damage
EMBO06
EMBO37
Fibroblasts - cytology
Fibroblasts - physiology
Humans
Intestines - cytology
Intestines - metabolism
Life span
Mice
Mice, Knockout
Mutation
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Scientific Report
Scientific Reports
senescence
Stem cells
Stem Cells - cytology
Stem Cells - physiology
Telomerase - genetics
Telomerase - metabolism
Telomere - metabolism
telomeres
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Summary:Telomere shortening limits the proliferation of primary human fibroblasts by the induction of senescence, which is mediated by ataxia telangiectasia mutated‐dependent activation of p53. Here, we show that CHK2 deletion impairs the induction of senescence in mouse and human fibroblasts. By contrast, CHK2 deletion did not improve the stem‐cell function, organ maintenance and lifespan of telomere dysfunctional mice and did not prevent the induction of p53/p21, apoptosis and cell‐cycle arrest in telomere dysfunctional progenitor cells. Together, these results indicate that CHK2 mediates the induction of senescence in fibroblasts, but is dispensable for the induction of telomere dysfunction checkpoints at the stem and progenitor cell level in vivo. This study provides evidence that CHK2‐independent checkpoints limit the function of stem and progenitor cells in response to telomere dysfunction.
ISSN:1469-221X
1469-3178
DOI:10.1038/embor.2010.83