Genetic control of mitotic spindle assembly and function

描述(由申请人提供)：本项目的长期目标是 了解有丝分裂纺锤体的功能是如何整合到细胞中的 酿酒酵母芽胞中的循环。磁盘轴检查点是 一种进化上保守的有丝分裂调控系统，当细胞在 染色体在有丝分裂纺锤体上没有正确排列。 纺锤体检查点基因的突变与基因组有关 人类的不稳定性和肿瘤进展。多种抗肿瘤化疗药物 像紫杉醇这样的试剂，通过激活细胞内的 主轴检查点。我们将使用遗传方法的组合来 确定单个染色体区域，即着丝粒在其中扮演的角色 主轴检查点。我们还将确定单个染色体是否 能够激活磁盘轴检查点，我们将确定角色 这种紧张感在激活过程中发挥作用。我们将使用一种人工合成的致命武器 使用屏幕了解磁盘轴检查点内存在的复杂性 小路。我们的实验将确定一些重要的监管 在多种细胞类型中控制基因组稳定性的机制。这个 纺锤体检查点基因可能识别化疗的分子靶点 对某些癌症和出生缺陷的干预。

DESCRIPTION (provided by applicant): The long-term goals of this project are to understand how the function of the mitotic spindle is integrated into the cell cycle in the budding yeast Saccharomyces cerevisiae. The spindle checkpoint is an evolutionarily conserved mitotic regulatory system that arrests cells when chromosomes are not properly aligned on the mitotic spindle apparatus. Mutations in spindle checkpoint genes have been implicated in genomic instability and tumor progression in humans. Various ant-tumor chemotherapeutic agents, like taxol, cause human cells to arrest in mitosis by activating the spindle checkpoint. We will use a combination of genetic approaches to determine the role that a single chromosome domain, the kinetochore, plays in the spindle checkpoint. We will also determine if a single chromosome is capable of activating the spindle checkpoint and we will determine the role that tension plays in the activation process. We will use a synthetic lethal screen with to explore the complexity that exists within the spindle checkpoint pathways. Our experiments will identify some of the important regulatory mechanisms that control genomic stability in a variety of cell types. The spindle checkpoint genes may identify molecular targets for chemotherapeutic intervention in some cancers and birth defects.