REVIEW Cell Research (2008): 17-26 DNA damage-induced cell death: lessons from the central nervous systemHelena Lobo Borges1,2, Rafael Linden3, Jean YJ Wang1 1Division of Hematology/Oncology, Moores Cancer Center, Department of Medicine, University of California, San Diego, 3855 Health Sciences, La Jolla, CA 92093-0820, USA; 2Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Cidade Universitária, 21940-590 Rio de Janeiro, Brazil; 3Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Cidade Universitária, 21940-590 Rio de Janeiro, Brazil
DNA damage can, but does not always, induce cell death. While several pathways linking DNA damage signals to mitochondria-dependent and -independent death machineries have been elucidated, the connectivity of these pathways is subject to regulation by multiple other factors that are not well understood. We have proposed two conceptual models to explain the delayed and variable cell death response to DNA damage: integrative surveillance versus autonomous pathways. In this review, we discuss how these two models may explain the in vivo regulation of cell death induced by ionizing radiation (IR) in the developing central nervous system, where the death response is regulated by radiation dose, cell cycle status and neuronal development. Cell Research (2008) 18:17-26. doi: 10.1038/cr.2007.110; published online 18 December 2007 Keywords: apoptosis, ATM, ionizing radiation, neonatal retina, neuroblasts, p53, phosphorylation |
copyright©2006 Institute of Biochemistry and Cell Biology,SIBS,CAS
ISSN:1001-0602(Print),1748-7838(Online);CN:31-1568
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