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

Abstract

Hair follicle stem cells have increased resistance to DNA damage-induced cell death. This is due to higher expression of Bcl2 and to a faster non-homologous end-joining (NHEJ) DNA repair activity, which attenuates p53 activation. 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.

Cite this article

Sotiropoulou, P., Candi, A., Mascré, G. et al. Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. Nat Cell Biol 12, 572–582 (2010). https://doi.org/10.1038/ncb2059

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