title: CHK2-independent induction of telomere dysfunction checkpoints in stem and progenitor cells.
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.
authors.affiliation: Department of Molecular Medicine, and Max Planck Research Group on Stem Cell Aging, University of Ulm, Ulm, Germany.
authors.forename: Kodandaramireddy
authors.initials: K
authors.lastname: Nalapareddy
authors.forename: Aaheli Roy
authors.initials: AR
authors.lastname: Choudhury
authors.forename: Anne
authors.initials: A
authors.lastname: Gompf
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ju
authors.forename: Satyavani
authors.initials: S
authors.lastname: Ravipati
authors.forename: Thomas
authors.initials: T
authors.lastname: Leucht
authors.forename: André
authors.initials: A
authors.lastname: Lechel
authors.forename: K Lenhard
authors.initials: KL
authors.lastname: Rudolph
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D019098:Telomerase