CHK2‐independent induction of telomere dysfunction checkpoints in stem and progenitor cells |
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Authors: | Kodandaramireddy Nalapareddy Anne Gompf Zhenyu Ju Satyavani Ravipati Thomas Leucht André Lechel K Lenhard Rudolph |
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Institution: | 1. Department of Molecular Medicine, and Max Planck Research Group on Stem Cell Aging, Albert Einstein alle 11, University of Ulm, Ulm, 89081 Germany;2. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Beijing, China |
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Abstract: | 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. |
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Keywords: | telomeres senescence stem cells CHK2 DNA damage |
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