Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development.
Gastrulation in mice is associated with the start of extreme proliferation and differentiation. The potential cost to the embryo of a very rapid proliferation rate is a high production of damaged cells. We demonstrate a novel surveillance mechanism for the elimination of cells damaged by ionizing radiation during mouse gastrulation. During this restricted developmental window, the embryo becomes hypersensitive to DNA damage induced by low dose irradiation (<0.5 Gy) and undergoes apoptosis without cell cycle arrest. Intriguingly, embryonic cells, including germ cell progenitors, but not extraembryonic cells, become hypersensitive to genotoxic stress and undergo Atm- and p53-dependent apoptosis. Thus, hypersensitivity to apoptosis in the early mouse embryo is a cell fate-dependent mechanism to ensure genomic integrity during a period of extreme proliferation and differentiation.
Heyer
B S
BS
Department of Anatomy, University of California, San Francisco, San Francisco, California 94143-0452 USA. Babette@itsa.ucsf.edu
MacAuley
A
A
Behrendtsen
O
O
Werb
Z
Z
D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D019070:Cell Lineage; D004249:DNA Damage; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005314:Embryonic and Fetal Development / Q000528:radiation effects; D005775:Gastrula / Q000528:radiation effects; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases