ATR功能破坏会导致染色体断裂和早期胚胎致死。
ATR disruption leads to chromosomal fragmentation and early embryonic lethality.
作者信息
Brown E J, Baltimore D
机构信息
California Institute of Technology, Division of Biology, Pasadena, California 91125 USA.
出版信息
Genes Dev. 2000 Feb 15;14(4):397-402.
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.
摘要
尽管在ATR(+/-)小鼠中观察到存活率略有下降和肿瘤发生率有所增加，但ATR(-/-)胚胎在发育早期即胚泡期之后、妊娠第7.5天之前死亡。在培养中，ATR(-/-)胚泡细胞继续循环进入有丝分裂2天，但随后无法扩张并死于半胱天冬酶依赖性凋亡。重要的是，在广泛凋亡之前，在ATR(-/-)细胞中观察到非半胱天冬酶依赖性染色体断裂，这意味着凋亡是由基因组完整性丧失引起的。这些数据表明，ATR对早期胚胎发育至关重要，并且必须在除调节p53之外的其他过程中发挥作用。
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