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Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death

(2010) NATURE CELL BIOLOGY. 12(6). p.572-582
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Abstract
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.
Keywords
STRAND BREAK REPAIR, RADIATION-INDUCED APOPTOSIS, SMALL-INTESTINE, SCID MUTATION, P53, MICE, SKIN, MOUSE, MECHANISMS, IRRADIATION

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Citation

Please use this url to cite or link to this publication:

Chicago
Sotiropoulou, Panagiota A, Aurelie Candi, Guilhem Mascre, Sarah De Clercq, Khalil Kass Youssef, Gaelle Lapouge, Ellen Dahl, et al. 2010. “Bcl-2 and Accelerated DNA Repair Mediates Resistance of Hair Follicle Bulge Stem Cells to DNA-damage-induced Cell Death.” Nature Cell Biology 12 (6): 572–582.
APA
Sotiropoulou, P. A., Candi, A., Mascre, G., De Clercq, S., Youssef, K. K., Lapouge, G., Dahl, E., et al. (2010). Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. NATURE CELL BIOLOGY, 12(6), 572–582.
Vancouver
1.
Sotiropoulou PA, Candi A, Mascre G, De Clercq S, Youssef KK, Lapouge G, et al. Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. NATURE CELL BIOLOGY. 2010;12(6):572–82.
MLA
Sotiropoulou, Panagiota A, Aurelie Candi, Guilhem Mascre, et al. “Bcl-2 and Accelerated DNA Repair Mediates Resistance of Hair Follicle Bulge Stem Cells to DNA-damage-induced Cell Death.” NATURE CELL BIOLOGY 12.6 (2010): 572–582. Print.
@article{998269,
  abstract     = {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.},
  author       = {Sotiropoulou, Panagiota A and Candi, Aurelie and Mascre, Guilhem and De Clercq, Sarah and Youssef, Khalil Kass and Lapouge, Gaelle and Dahl, Ellen and Semeraro, Claudio and Denecker, Geertrui and Marine, Jean-Christophe and Blanpain, Cedric},
  issn         = {1465-7392},
  journal      = {NATURE CELL BIOLOGY},
  keyword      = {STRAND BREAK REPAIR,RADIATION-INDUCED APOPTOSIS,SMALL-INTESTINE,SCID MUTATION,P53,MICE,SKIN,MOUSE,MECHANISMS,IRRADIATION},
  language     = {eng},
  number       = {6},
  pages        = {572--582},
  title        = {Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death},
  url          = {http://dx.doi.org/10.1038/ncb2059},
  volume       = {12},
  year         = {2010},
}

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