• Medientyp: E-Artikel
  • Titel: DNA damage in stem cells activates p21, inhibits p53, and induces symmetric self-renewing divisions
  • Beteiligte: Insinga, Alessandra; Cicalese, Angelo; Faretta, Mario; Gallo, Barbara; Albano, Luisa; Ronzoni, Simona; Furia, Laura; Viale, Andrea; Pelicci, Pier Giuseppe
  • Erschienen: Proceedings of the National Academy of Sciences, 2013
  • Erschienen in: Proceedings of the National Academy of Sciences, 110 (2013) 10, Seite 3931-3936
  • Sprache: Englisch
  • DOI: 10.1073/pnas.1213394110
  • ISSN: 0027-8424; 1091-6490
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  • Beschreibung: DNA damage leads to a halt in proliferation owing to apoptosis or senescence, which prevents transmission of DNA alterations. This cellular response depends on the tumor suppressor p53 and functions as a powerful barrier to tumor development. Adult stem cells are resistant to DNA damage-induced apoptosis or senescence, however, and how they execute this response and suppress tumorigenesis is unknown. We show that irradiation of hematopoietic and mammary stem cells up-regulates the cell cycle inhibitor p21, a known target of p53, which prevents p53 activation and inhibits p53 basal activity, impeding apoptosis and leading to cell cycle entry and symmetric self-renewing divisions. p21 also activates DNA repair, limiting DNA damage accumulation and self-renewal exhaustion. Stem cells with moderate DNA damage and diminished self-renewal persist after irradiation, however. These findings suggest that stem cells have evolved a unique, p21-dependent response to DNA damage that leads to their immediate expansion and limits their long-term survival.
  • Zugangsstatus: Freier Zugang