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ATR disruption leads to chromosomal fragmentation and early embryonic lethality

Brown, Eric J. and Baltimore, David (2000) ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes and Development, 14 (4). pp. 397-402. ISSN 0890-9369. PMCID PMC316378. doi:10.1101/gad.14.4.397.

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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.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 2000 by Cold Spring Harbor Laboratory Press. Received November 16, 1999; revised version accepted January 10, 2000. We are indebted to M. Scott and J. Harrison for invaluable assistance in the generation of knockout cells and chimeric ATR^(+/−) mice. We also thank the following people for reagents, technical training, and helpful discussions: K. Cimprich, S. Schreiber, A. Koleske, C. Lois, J. Pomerantz, Y. Yamanashi, J. Baer, I. Stancovski, H. Chang, Y. Xu, S. Cherry, M. Meffert, and M. Porteus. We are grateful to P. Svec and L. Newman for laboratory assistance and L. Anonuevo, K. Owler, B. Kennedy, and S. Pease. E.J.B. was supported by a fellowship from the Cancer Research Institute. The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC section 1734 solely to indicate this fact.
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Cancer Research InstituteUNSPECIFIED
Subject Keywords:ATR; ATM; p53; embryonic lethality; chromosome breaks
Issue or Number:4
PubMed Central ID:PMC316378
Record Number:CaltechAUTHORS:20200506-104739180
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103030
Deposited By: Tony Diaz
Deposited On:06 May 2020 17:56
Last Modified:16 Nov 2021 18:17

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