Mitotic Catastrophe and the Mitotic Exit DNA Damage Checkpoint

有丝分裂灾难和有丝分裂退出 DNA 损伤检查点

• 批准号: 7094837
• 负责人: PUMIN ZHANG
• 金额: $ 26.63万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-26 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094837
• 关键词: DNA damage; cell cycle; genome

DESCRIPTION (provided by applicant): The impact of DNA damage on cell cycle progression is cell cycle stage dependent. In mitosis, DNA damage induces mitotic catastrophe which is manifested as either cell death or failure of cytokinesis. The latter leads to the formation of binucleated cells and cell cycle arrest in Gl state via the p53-dependent tetraploid checkpoint. It is not clear whether the failure of cytokinesis is a result of mechanical problems associated with the damaged DNA or is a regulated process. Recently, we discovered the presence of a mitotic exit DNA damage checkpoint in mammalian cells that prevents cytokinesis. We propose that this checkpoint is responsible for mitotic catastrophe and functions as the last line of defense in preserving genome stability. We will identify mechanisms used by the checkpoint to stop mitosis and to induce mitotic catastrophe, and will determine the physiological significance of this checkpoint.

描述(申请人提供)：DNA损伤对细胞周期进程的影响取决于细胞周期阶段。在有丝分裂中，DNA损伤导致有丝分裂灾难，表现为细胞死亡或胞质分裂失败。后者通过P53依赖的四倍体检查点导致双核细胞的形成和细胞周期停滞在Gl状态。目前尚不清楚细胞质分裂的失败是与受损的DNA相关的机械问题造成的，还是一个受监管的过程。最近，我们发现在哺乳动物细胞中存在一个有丝分裂出口DNA损伤检查点，它可以阻止细胞质分裂。我们认为这个检查点是有丝分裂灾难的罪魁祸首，是维持基因组稳定性的最后一道防线。我们将确定检查点用于停止有丝分裂和诱导有丝分裂灾难的机制，并将确定该检查点的生理意义。