ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Eric J. Brown and David Baltimore report that ATR-deficient embryos die early in development, while ATR+/− mice show a slight decrease in survival and increased tumor incidence. ATR is essential for early embryonic development and functions beyond p53 regulation. ATR disruption causes chromosomal fragmentation and caspase-dependent apoptosis in blastocysts, indicating genomic integrity loss. ATR and ATM have overlapping but non-redundant roles in p53 regulation. ATR is required for early embryonic cell proliferation and DNA damage response. ATR-deficient cells exhibit chromosomal fragmentation, suggesting loss of genomic integrity. ATR may regulate BRCA gene products and S-to-M phase transition in early embryos. ATR disruption leads to early embryonic lethality and increased tumor incidence in heterozygous mice. ATR is essential for preventing DNA damage during embryogenesis. ATR may be involved in DNA replication checkpoints and prevent mitotic catastrophe. ATR functions in DNA repair and cell cycle regulation, and its disruption leads to chromosomal fragmentation and early embryonic death. ATR is essential for embryonic development and may play a role in tumor suppression. The study highlights the importance of ATR in maintaining genomic stability and embryonic development.ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Eric J. Brown and David Baltimore report that ATR-deficient embryos die early in development, while ATR+/− mice show a slight decrease in survival and increased tumor incidence. ATR is essential for early embryonic development and functions beyond p53 regulation. ATR disruption causes chromosomal fragmentation and caspase-dependent apoptosis in blastocysts, indicating genomic integrity loss. ATR and ATM have overlapping but non-redundant roles in p53 regulation. ATR is required for early embryonic cell proliferation and DNA damage response. ATR-deficient cells exhibit chromosomal fragmentation, suggesting loss of genomic integrity. ATR may regulate BRCA gene products and S-to-M phase transition in early embryos. ATR disruption leads to early embryonic lethality and increased tumor incidence in heterozygous mice. ATR is essential for preventing DNA damage during embryogenesis. ATR may be involved in DNA replication checkpoints and prevent mitotic catastrophe. ATR functions in DNA repair and cell cycle regulation, and its disruption leads to chromosomal fragmentation and early embryonic death. ATR is essential for embryonic development and may play a role in tumor suppression. The study highlights the importance of ATR in maintaining genomic stability and embryonic development.