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：
10631812
负责人：
Needhi Bhalla
金额：
$ 8.17万
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：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2024-07-31
项目状态：
已结题

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 abnormalities 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?

项目摘要精确控制染色体隔离，以确保子细胞获得正确的数量染色体。通过监测染色体，细胞周期检查点在该调节中起重要作用行为并延迟或阻止细胞周期以纠正错误。尽管几乎被描述了仅在单个单元格中，细胞周期检查点的函数可能在多细胞中最关键染色体异常可以产生癌症，不育症，流产和先天缺陷的生物体。随着多细胞生物的发展，细胞的大小，形状，命运，染色体会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与调制和调制协调通过这些细胞环境中的这些变化，未知。我们已经表明，在一种生物环境中的检查点蛋白可以监测和调节根本不同在不同的生物学背景下的染色体行为。通过分析必需品的功能和调节秀丽隐杆线虫中大小，形状，命运和组织变化的细胞中的检查点因子，我们将确定机制，共同和独特的，可以保证染色体在所有细胞类型中都正确分离。从根本上讲，我们未来的工作重点是解决两个主要问题：检查站的功能是否存在蛋白质因其生物学上下文而异，因此相同的蛋白质似乎具有巨大的不同的角色？或是否有常见的基本机制来监测各种染色体行为产生功能不同的检查点响应？