Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development.

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Heyer BS,MacAuley A,Behrendtsen O,Werb Z

subject

Has Abstract

pub_date

2000-08-15 00:00:00

pages

2072-84

issue

16

eissn

0890-9369

issn

1549-5477

journal_volume

14

pub_type

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