Cell cycle checkpoint control in C. elegans

线虫细胞周期检查点控制

基本信息

批准号：
10726915
负责人：
Needhi Bhalla
金额：
$ 8.91万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-03 至 2026-05-31
项目状态：
未结题

项目摘要

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?

项目概要精确控制染色体分离，以确保子细胞接受正确数量的染色体染色体。细胞周期检查点通过监测染色体在这种调节中发挥重要作用行为并延迟或阻止细胞周期以纠正错误。尽管被描述为几乎仅在单细胞中，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、流产和出生缺陷。随着多细胞生物的发展，细胞的大小、形状、命运、染色体发生巨大变化结构和细胞周期持续时间。细胞周期检查点的功能如何协调和调节细胞环境中的这些变化是未知的。我们已经证明，一种生物环境中的检查点蛋白可以监测和调节完全不同的不同生物背景下的染色体行为。通过分析必要的功能和调节线虫中细胞大小、形状、命运和组织各不相同的检查点因子，我们将确定机制，既常见又独特，保证染色体在所有细胞类型中正确分离。从根本上说，我们未来的工作重点是解决两个主要问题：检查点的功能是否有效？蛋白质根据其生物学背景而变化，因此相同的蛋白质似乎具有显着的变化不同的角色？或者是否存在监测不同染色体行为的共同基本机制产生功能上不同的检查点响应？