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SPINDLE POLES AND NUCLEAR PORES--YEAST NDC1 AND MPS2

纺锤体极和核孔--酵母NDC1和MPS2

基本信息

批准号：
6636351
负责人：
MARK WINEY
金额：
$ 21.69万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-04-01 至 2005-03-31
项目状态：
已结题

项目摘要

Spindle pole body (SPB) duplication during the budding yeast cell cycle is a critical and essential event in assembly of the mitotic spindle that ultimately segregates the chromosomes to the progeny cells. In yeast, the SPB is the sole microtubule organizing center and is embedded in the nuclear envelope (NE) nucleating microtubules in the nucleoplasm and in the cytoplasm. Failure in SPB duplication or in SPB function leads to anueploidy and polyploidy similar to that observed in many cancer cells. This proposal addresses the function of two genes, NDC1 and MPS2, that are required during SPB duplication to insert the new SPB into the NE. We have found that these essential genes encode membrane proteins that localize to the SPB. In addition, Ndc1p is found in nuclear pore complexes (NPC) and Mps2p is found in the NE and the ER membranes. NPCs, like SPBs, are embedded in the NE. The aims of this proposal are to first, explore the function of Ndc1p and Mps2p in SPB duplication by looking for genetic and physical interactions with other SPB components. We will also carry out genetic screens to look for additional genes that function in SPB duplication. Second, we will determine the topology of Ndc1p and Mps2p in the nuclear envelope. Furthermore, we will determine whether these proteins have access to the nucleoplasm and/or the cytoplasm as part of our efforts to determine how they function. Third, we will study the NPC-related function of Ndc1p. We believe that Ndc1p may be required for NPC assembly, like SPB assembly. We propose a variety of genetic, cytological and biochemical approaches to discover the role of Ndc1p at NPCs and to identify proteins with which it collaborates in this function. Finally, we have identified a novel gene, NOE1, that is required for the viability of ndc1-1 cells and whose product may be localized to the SPB, suggesting a possible role for Noe1p in SPB duplication. We will define the role of Noe1p with respect to Ndc1p, and identify genes that interact with NOE1. The proposed project is aimed at understanding the function of a set of unusual membrane proteins at the SPB and the NPC, and at identifying other proteins with which the interact at these organelles.

芽殖酵母细胞周期中的纺锤体极体（SPB）复制是有丝分裂纺锤体组装过程中的一个关键且重要的事件，最终将染色体分离到子代细胞。在酵母中，SPB 是唯一的微管组织中心，嵌入核质和细胞质中的核膜 (NE) 成核微管中。 SPB 复制或 SPB 功能失败会导致非整倍体和多倍体，类似于在许多癌细胞中观察到的情况。该提案解决了两个基因 NDC1 和 MPS2 的功能，这两个基因是 SPB 复制期间将新 SPB 插入 NE 所需的。我们发现这些必需基因编码定位于 SPB 的膜蛋白。此外，Ndc1p 存在于核孔复合物 (NPC) 中，Mps2p 存在于 NE 和 ER 膜中。 NPC 与 SPB 一样，嵌入在 NE 中。该提案的目的是首先通过寻找与其他 SPB 成分的遗传和物理相互作用来探索 Ndc1p 和 Mps2p 在 SPB 复制中的功能。我们还将进行遗传筛选，寻找在 SPB 复制中起作用的其他基因。其次，我们将确定 Ndc1p 和 Mps2p 在核膜中的拓扑结构。此外，我们将确定这些蛋白质是否能够进入核质和/或细胞质，作为我们确定它们如何发挥作用的努力的一部分。第三，我们将研究Ndc1p的NPC相关功能。我们认为 Ndc1p 可能是 NPC 组装所必需的，就像 SPB 组装一样。我们提出了多种遗传、细胞学和生化方法来发现 Ndc1p 在 NPC 中的作用，并鉴定与其协同发挥此功能的蛋白质。最后，我们鉴定了一个新基因 NOE1，它是 ndc1-1 细胞生存所需的，其产物可能定位于 SPB，这表明 Noe1p 在 SPB 复制中可能发挥作用。我们将定义 Noe1p 相对于 Ndc1p 的作用，并识别与 NOE1 相互作用的基因。拟议的项目旨在了解 SPB 和 NPC 中一组不寻常的膜蛋白的功能，并鉴定与这些细胞器相互作用的其他蛋白质。