Nature cell biology, 2010-06, Vol.12 (6), p.572-582
2010
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Details
- Autor(en) / Beteiligte
- Titel
- Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death
- Ist Teil von
- Nature cell biology, 2010-06, Vol.12 (6), p.572-582
- Ort / Verlag
- England
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Adult stem cells (SCs) are at high risk of accumulating deleterious mutations because they reside and self-renew in adult tissues for extended periods. Little is known about how adult SCs sense and respond to DNA damage within their natural niche. Here, using mouse epidermis as a model, we define the functional consequences and the molecular mechanisms by which adult SCs respond to DNA damage. We show that multipotent hair-follicle-bulge SCs have two important mechanisms for increasing their resistance to DNA-damage-induced cell death: higher expression of the anti-apoptotic gene Bcl-2 and transient stabilization of p53 after DNA damage in bulge SCs. The attenuated p53 activation is the consequence of a faster DNA repair activity, mediated by a higher non-homologous end joining (NHEJ) activity, induced by the key protein DNA-PK. Because NHEJ is an error-prone mechanism, this novel characteristic of adult SCs may have important implications in cancer development and ageing.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1465-7392eISSN: 1476-4679DOI: 10.1038/ncb2059Titel-ID: cdi_pubmed_primary_20473297
- Format
- –
- Schlagworte
- Adult, Aging, Animals, Biochemical Phenomena, Cell Death, DNA - metabolism, DNA Damage, DNA Repair, Epidermis - metabolism, Hair Follicle - cytology, Hair Follicle - metabolism, Hair Follicle - physiology, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Knockout, Mice, SCID, Multipotent Stem Cells - cytology, Multipotent Stem Cells - metabolism, Multipotent Stem Cells - physiology, Stem Cells - metabolism, Tumor Suppressor Protein p53 - metabolism