ATR disruption leads to chromosomal fragmentation and early embryonic lethality

EJ Brown, D Baltimore - Genes & development, 2000 - genesdev.cshlp.org
EJ Brown, D Baltimore
Genes & development, 2000genesdev.cshlp.org
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 pc 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 in ATR−/− cells prior to
widespread apoptosis, implying that apoptosis is caused by a loss of genomic integrity …
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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