ATR disruption leads to chromosomal fragmentation and early embryonic lethality
Abstract
Although a small decrease in survival and increase in tumor incidence was observed in ATR +/−mice, ATR −/− embryos die early in development, subsequent to the blastocyst stage and prior to 7.5 days p.c. In culture, ATR −/−blastocysts cells continue to cycle into mitosis for 2 days but subsequently fail to expand and die of caspase-dependent apoptosis. Importantly, caspase-independent chromosome breaks are observed inATR −/− cells prior to widespread apoptosis, implying that apoptosis is caused by a loss of genomic integrity. These data show that ATR is essential for early embryonic development and must function in processes other than regulation of p53.
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↵1 Corresponding author.
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E-MAIL baltimo{at}caltech.edu; FAX (626) 585-9495.
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- Received November 16, 1999.
- Accepted January 10, 2000.
- Cold Spring Harbor Laboratory Press