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7235146 
Journal Article 
DNA Damage, Checkpoint Responses, and Cell Cycle Control in Aging Stem Cells 
Kleinhans, KN; Burkhalter, MD; , 
2012 
KARGER 
BASEL 
36-+ 
WOS:000317550900005 
A multitude of sources induce lesions in cellular DNA. If left unrepaired, these DNA damages have the potential to trigger mutations and chromosomal aberrations that can initiate carcinogenesis. Cellular surveillance systems sense the presence of DNA damage and induce DNA damage checkpoints, which in turn trigger a halt of the cell cycle and recruit the appropriate DNA repair factors. Several repair pathways have evolved, each of which reverts a specific subset of chemically distinct DNA lesions. If the damage load is too high, the checkpoint cascade can induce a permanent cell cycle arrest (senescence) or alternatively induce apoptosis to remove damaged cells. Thus, DNA damage checkpoints and repair pathways are key elements maintaining genome integrity and preventing carcinogenesis. As a downside, the activation of these checkpoints may accelerate tissue aging. In recent years, it has become evident that DNA damage accumulates in aging stem cells. Several speakers at the Else Kroner-Fresenius Symposium on the Molecular Mechanisms of Stem Cell Aging shared their novel data to shed light on the molecular basis of this process and focused on the following specific topics: (1) hair follicle stem cells are resistant to irradiation-induced apoptosis due to quicker repair of DNA lesions as well as upregulation of anti-apoptotic factors, (2) the polycomb repressor group gene Bmi1 has a novel role in the repair of DNA double strand breaks by stimulating homologous recombination, (3) the mixed-lineage-leukemia-like (MLL)-4 complex mediates aging mechanisms by increasing myeloid lineage potential as well as cellular stress levels, and (4) DNA damage induces lymphoid differentiation of hematopoietic stem cells via activation of the transcription factor BATF. Copyright (C) 2012 S. Karger AG, Basel 
Rudolph, KL; 
978-3-318-02170-7 
3rd Else Kroner-Fresenius Symposium 
Gunzburg, GERMANY