Bcl-2 and Accelerated DNA Repair Mediates Resistance of Hair Follicle Bulge Stem Cells to DNA-damage-induced Cell Death

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2010 May 18

PMID 20473297

Citations 122

Authors

Panagiota A Sotiropoulou

Aurelie Candi

Guilhem Mascre

Sarah De Clercq

Khalil Kass Youssef

Gaelle Lapouge

Ellen Dahl

Claudio Semeraro

Geertrui Denecker

Jean-Christophe Marine

Cedric Blanpain

Affiliations

Soon will be listed here.

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.

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