ATR disruption leads to chromosomal fragmentation and early embryonic lethality

Although a small decrease in survival and increase in tumor incidence was o bserved in ATR(+/-) mice, ATR(-/-) embryos die early in development, subseq uent 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 subsequen tly fail to expand and die of caspase dependent apoptosis. Importantly, cas pase-independent chromosome breaks are observed in ATR-cells prior to wides pread apoptosis, implying that apoptosis is caused by a loss of genomic int egrity. These data show that ATR is essential for early embryonic developme nt and must function in processes other than regulation of p53.