DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint
DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint
复制标题
DOI：
10.1073/pnas.0409130102
复制
发表时间：
2005-01-25
影响因子：
11.1
通讯作者：
Zhang, PM
中科院分区：
文献类型：
--
作者：
Huang, XX;Tran, T;Zhang, PM
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。为了响应DNA损伤，检查点被激活以延迟细胞周期进程并协调修复。处于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。目前还不清楚是否有丝分裂灾难中的有丝分裂的终止是由DNA损伤检查点调节。在这里，我们报告了哺乳动物细胞中存在有丝分裂出口DNA损伤检查点。该检查点延迟有丝分裂退出并阻止胞质分裂，从而导致有丝分裂灾难。DNA损伤诱导的有丝分裂出口延迟与Cdh 1激活的抑制和细胞周期蛋白B1的衰减降解相关。我们证明了检查点是Chk1依赖的。
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.