Cell cycle checkpoint control in C. elegans

项目摘要 染色体分离受到精确控制，以确保子代细胞获得正确数量的 染色体。细胞周期检查点通过监测染色体在这一调节中发挥重要作用 行为和延迟或阻止细胞周期以纠正错误。尽管被描述成几乎 仅在单细胞中，细胞周期检查点的功能在多细胞中可能是最关键的 染色体异常会导致癌症、不孕不育、流产和出生缺陷。 随着多细胞生物的发展，细胞在大小、形状、命运、染色体等方面都发生了巨大的变化。 结构和细胞周期持续时间。细胞周期检查点的功能是如何协调和调节的 这些细胞环境的变化是未知的。 我们已经证明，在一种生物背景下，检查点蛋白可以监控和调节截然不同的不同 染色体在不同生物背景下的行为。通过分析Essential的功能和调节 线虫细胞中不同大小、形状、命运和组织的检查点因子，我们将确定其机制， 共同的和独特的，这保证了染色体在所有类型的细胞中正确分离。 从根本上说，我们未来的工作重点是解决两个主要问题：检查点的功能 蛋白质因其生物环境的不同而不同，因此相同的蛋白质似乎具有显著的 不同的角色？或者有没有共同的基本机制来监控不同的染色体行为 产生功能不同的检查点响应？

Project Summary Chromosome segregation is precisely controlled to ensure that daughter cells receive the correct number of chromosomes. Cell cycle checkpoints play an important role in this regulation by monitoring chromosome behavior and delaying or arresting the cell cycle to correct errors. Despite being characterized almost exclusively in single cells, the functions of cell cycle checkpoints are perhaps most critical in multicellular organisms, where chromosomal abnormailities can produce cancer, infertility, miscarriages and birth defects. As multicellular organisms develop, cells undergo dramatic changes in size, shape, fate, chromosome structure and cell cycle duration. How the function of cell cycle checkpoints is coordinated with and modulated by these changes in cellular context are unknown. We have shown that checkpoint proteins in one biological context can monitor and regulate radically different chromosome behaviors in a different biological context. By analyzing the function and regulation of essential checkpoint factors in cells that vary in size, shape, fate, and tissue in C. elegans, we will identify mechanisms, both common and unique, that guarantee that chromosomes segregate properly in all cell types. Fundamentally, our future work is focused on addressing two major questions: Does the function of checkpoint proteins vary depending on their biological context, such that the same proteins appear to have dramatically different roles? Or are there common fundamental mechanisms that monitor diverse chromosome behaviors to produce functionally different checkpoint responses?