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

Nat Cell Biol. 2010 Jun;12(6):572-82. doi: 10.1038/ncb2059. Epub 2010 May 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Tumor Suppressor Protein p53
  • DNA