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 in ATR(-/-) 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Ataxia Telangiectasia Mutated Proteins
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BRCA1 Protein / physiology
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BRCA2 Protein
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Blastocyst / pathology
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Caspases / metabolism
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Cell Cycle Proteins*
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Cell Transformation, Neoplastic / genetics
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Chromosome Aberrations*
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DNA Repair / genetics
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Fetal Death / genetics*
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Gene Expression Regulation, Developmental*
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Gene Targeting
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Genotype
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitosis
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Neoplasm Proteins / physiology
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Neoplasms, Experimental / genetics
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / physiology*
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Transcription Factors / physiology
Substances
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BRCA1 Protein
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BRCA2 Protein
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Cell Cycle Proteins
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Neoplasm Proteins
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Transcription Factors
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Atr protein, mouse
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases
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Caspases