Mitotic regulation by checkpoints in budding yeast

芽殖酵母中检查点的有丝分裂调节

基本信息

批准号：
8318164
负责人：
Daniel J Burke
金额：
$ 32.04万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-28 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8318164
关键词：
Address Anaphase Aneuploidy Biochemical Markers Biochemistry Cell Cycle Cells Cellular biology Chromosome Segregation Chromosomes Congenital Abnormality DNA Damage Data Development Disease Genes Genetic Genetic Screening Genome Stability Genomic Instability Goals Health Homologous Gene Human Kinetochores Malignant Neoplasms Maps Measures Microtubules Mitosis Mitotic Modeling Monitor Nuclear Pore Complex Pathway interactions Phospho-Specific Antibodies Phosphorylation Process Proteins Recruitment Activity Regulation Regulatory Pathway Research Resolution Role Saccharomyces cerevisiae Saccharomycetales Signal Transduction Sister Chromatid Site Source System Testing abstracting driving force gene function improved in vivo insight loss of function member molecular marker mutant novel prevent research study response role model segregation transmission process tumor

项目摘要

Abstract Errors in chromosome segregation are the major source of aneuploidy and a driving force in the development of tumors. The spindle assembly checkpoint (SAC) is one of the mechanisms that prevents aneuploidy and is an important regulator of genomic stability. The SAC is orchestrated by the kinetochore and a major unresolved problem, addressed in this proposal, is to determine how the kinetochore measures the lack of tension and lack of occupancy and how the kinetochore transfers that information to the cell cycle machinery. We will complete high resolution mapping of the tension branch of the SAC within the kinetochore using loss-of- function mutants. We have developed a phospho-specific antibody to Mad3 that is the first biochemical marker for the tension branch of the SAC and we propose to use it to dissect this important component of SAC regulation. We propose a new model for the role of the kinetochore in the tension checkpoint. We will determine if subsets of Mad3-containing proteins are phosphorylated, where Mad3 is phosphorylated in the cell and which kinetochore proteins are needed to transmit the tension signal. We have isolated novel mutants that are specific to the occupancy branch of the SAC. We will dissect the role for the SAC in the DNA damage pathway which requires Mec1 and Tel1 phosphorylation of SAC proteins and represents a novel pathway of mitotic regulation. Together, the experiments in this proposal will provide important insights into how SAC signaling is initiated and integrated into the cell cycle.

抽象的染色体分离错误是非整倍体的主要来源，也是非整倍体的驱动力。肿瘤的发展。主轴装配检查点 (SAC) 是一种机制防止非整倍性，是基因组稳定性的重要调节因子。 SAC精心策划由着丝粒和本提案中解决的一个主要未解决问题是确定着丝粒如何测量缺乏张力和缺乏占用以及如何着丝粒将该信息传递给细胞周期机器。我们将完成高使用损失来绘制动粒内 SAC 张力分支的分辨率图功能突变体。我们开发了一种针对 Mad3 的磷酸化特异性抗体，这是第一个 SAC 张力分支的生化标记，我们建议用它来剖析它 SAC监管的重要组成部分。我们提出了一个新的角色模型着丝粒位于张力检查点。我们将确定是否包含 Mad3 的蛋白质子集被磷酸化，其中 Mad3 在细胞中被磷酸化，哪些动粒蛋白被磷酸化需要传输张力信号。我们分离出了特异于的新型突变体 SAC 的占用部门。我们将剖析 SAC 在 DNA 损伤中的作用该途径需要 SAC 蛋白的 Mec1 和 Tel1 磷酸化，代表了一种新的途径有丝分裂调控途径。总之，本提案中的实验将提供重要的深入了解 SAC 信号传导如何启动并整合到细胞周期中。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A redundant function for the N-terminal tail of Ndc80 in kinetochore-microtubule interaction in Saccharomyces cerevisiae.

酿酒酵母着丝粒-微管相互作用中 Ndc80 N 末端尾部的冗余功能。

DOI：
10.1534/genetics.112.143818
发表时间：
2012
期刊：
Genetics
影响因子：
3.3
作者：
Demirel,PinarB;Keyes,BriceE;Chaterjee,Mandovi;Remington,CourtneyE;Burke,DanielJ
通讯作者：
Burke,DanielJ

Sister chromatids segregate at mitosis without mother-daughter bias in Saccharomyces cerevisiae.

酿酒酵母中姐妹染色单体在有丝分裂时分离，不存在母女偏差。