ATR disruption leads to chromosomal fragmentation and early embryonic lethality.

By E. Brown, David Baltimore. Genes & Development, 2000

1,030 citations recorded by the source corpus.

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.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/9cfc8d22c69b43fad49c5261ba9fabd0a724ca78

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Citations in the corpus

• ATR: An Essential Regulator of Genome Integrity (2008, neutral): “However, ATR is essential for the viability of replicating human and mouse cells, whereas ATM is no”
• Surviving the breakup: the DNA damage checkpoint. (2006, background): “Mammalian ATR is also essential for cell viability (14, 30), though whether this reflects a conserved role in fork stabilization or RNR regulation is unknown.”
• A splicing mutation affecting expression of ataxia–telangiectasia and Rad3–related protein (ATR) results in Seckel syndrome (2003, background): “The severity of this hypomorphic mutation is shown by the marked microcephaly and dwarfism observed in affected individuals and is consistent with the embryonic and somatic lethality seen in the absence of AT”
• Toward maintaining the genome: DNA damage and replication checkpoints. (2002, background): “The ATM protein kinase, orthologous to Tel1 in both budding and fission yeast, has been studied more extensively than ATR for two reasons: ( a) in 1995, ATM was identified as the gene defective in the syndrome AT, whereas no association between ATR deficiency and a disease yet exists, and ( b) unlik”
• Pathways of apoptotic and non-apoptotic death in tumour cells (2004, background): “The inhibition or inactivation of any of these G2-checkpoint genes — including those that encode AT”
• Autophagy suppresses tumor progression by limiting chromosomal instability. (2007, methodology): “5 μg/mL) and metaphase chromosomes were prepared (Brown and Baltimore 2000).”
• P53 Binding Protein 1 (53bp1) Is an Early Participant in the Cellular Response to DNA Double-Strand Breaks (2000, background): “The Journal of Cell Biology, Volume 151, 2000 1382 be determined (Brown and Baltimore, 2000).”
• ATM and related protein kinases: safeguarding genome integrity (2003, background): “Involvement in such a crucial process might explain why, unlike ATM, loss of ATR is embryonic-lethal in mic”
• ATR-Mediated Checkpoint Pathways Regulate Phosphorylation and Activation of Human Chk1 (2001, background): “Like ATR, Chk1 has been shown to be an essential gene in mice (6, 17, 44, 61).”