Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death.
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.
Sotiropoulou
Panagiota A
PA
Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles (ULB), 808, route de Lennik, BatC, C6-130, 1070 Brussels, Belgium.
Candi
Aurélie
A
Mascré
Guilhem
G
De Clercq
Sarah
S
Youssef
Khalil Kass
KK
Lapouge
Gaelle
G
Dahl
Ellen
E
Semeraro
Claudio
C
Denecker
Geertrui
G
Marine
Jean-Christophe
JC
Blanpain
Cédric
C
D000328:Adult; D000375:Aging; D000818:Animals; D001669:Biochemical Phenomena; D016923:Cell Death; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004817:Epidermis / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D004247:DNA
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