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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint.
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DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint.

机译：DNA损伤诱导的有丝分裂灾难由Chk1依赖性有丝分裂出口DNA损伤检查点介导。

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摘要

Mitotic catastrophe is the response of mammalian cells to mitotic DNA damage. It produces tetraploid cells with a range of different nuclear morphologies from binucleated to multimicronucleated. In response to DNA damage, checkpoints are activated to delay cell cycle progression and to coordinate repair. Cells in different cell cycle phases use different mechanisms to arrest their cell cycle progression. It has remained unclear whether the termination of mitosis in a mitotic catastrophe is regulated by DNA damage checkpoints. Here, we report the presence of a mitotic exit DNA damage checkpoint in mammalian cells. This checkpoint delays mitotic exit and prevents cytokinesis and, thereby, is responsible for mitotic catastrophe. The DNA damage-induced mitotic exit delay correlates with the inhibition of Cdh1 activation and the attenuated degradation of cyclin B1. We demonstrate that the checkpoint is Chk1-dependent.
机译：有丝分裂灾难是哺乳动物细胞对有丝分裂DNA损伤的反应。它产生具有从双核到多微核的一系列不同核形态的四倍体细胞。响应DNA损伤，激活检查点以延迟细胞周期进程并协调修复。不同细胞周期阶段的细胞使用不同的机制来阻止其细胞周期进程。尚不清楚DNA损伤检查点是否能控制有丝分裂灾难中有丝分裂的终止。在这里，我们报告哺乳动物细胞中有丝分裂出口DNA损伤检查点的存在。该检查点延迟了有丝分裂的退出并阻止了胞质分裂，从而导致了有丝分裂的灾难。 DNA损伤诱导的有丝分裂退出延迟与Cdh1激活的抑制和细胞周期蛋白B1的降解减弱有关。我们证明了检查点是依赖Chk1的。

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