Role of the central kinetochore in chromosome segregation

中央动粒在染色体分离中的作用

• 批准号: 262246-2008
• 负责人: Vogel, Jackie
• 金额: $ 2.33万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=498083
• 关键词: Role; central; kinetochore; chromosome; segregation

The transmission of genetic information during cell division requires the coordination of three critical events; first, the attachment of chromosomes to the microtubules of the mitotic spindle, second the application of forces that pull chromosomes towards the poles of the cell and away from spindle mid-zone and third, the coordination of completion of these events with the onset of cytokinesis. The kinetochore is a complex structure of proteins that is associated with the centromeres of chromosomes. While the structure and organization of the centromere and kinetochore is diverse among eukaryotes, they play an evolutionarily conserved and central role in attaching chromosomes to microtubules in all cell types. Chromosome attachment, or bi-orientation, is an error prone process. The kinetochore is not only required to segregate the chromosomes, but also to report the status of attachment. Bi-orientation of all the chromosomes results in tension on the spindle, and is required for entry into anaphase. Defects in bi-orientation result in lack of tension on the spindle, and are reported locally; a defect at one chromosome is sufficient to trigger a) the repair of defective attachments, and if repair is incomplete b) activation of a cell cycle checkpoint that delays entry into anaphase. The mechanism of repair, and the requirement for the kinetochore for in checkpoint activation is well established. Once the checkpoint is activated, the cell cycle delay must be maintained until all attachments have been repaired. In the last several years, proteins of the central kinetochore (CK) have emerged as candidates for coordinating repair with checkpoint control. However, the mechanism by which repair and checkpoint functions are coupled is less understood. The goal of this project is to understand how the repair and checkpoint functions of CK proteins are controlled in cells.

在细胞分裂过程中遗传信息的传递需要三个关键事件的协调;第一，染色体附着到有丝分裂纺锤体的微管上，第二，施加力将染色体拉向细胞的两极并远离纺锤体中间区，第三，这些事件的完成与胞质分裂的开始的协调。动粒是与染色体的着丝粒相关的蛋白质的复杂结构。虽然着丝粒和动粒的结构和组织在真核生物中是不同的，但它们在所有细胞类型中将染色体附着到微管中起着进化上保守的核心作用。染色体附着或双向定位是一个容易出错的过程。动粒不仅需要分离染色体，而且还需要报告附着状态。所有染色体的双向取向导致纺锤体上的张力，并且是进入后期所必需的。双向缺陷导致纺锤体上缺乏张力，并在局部报告;一条染色体上的缺陷足以触发a）修复有缺陷的附着，如果修复不完全，则B）激活延迟进入后期的细胞周期检查点。修复的机制，以及在检查点激活的动粒的要求是很好的建立。一旦检查点被激活，必须维持细胞周期延迟，直到所有附着都被修复。 在过去的几年中，中央动粒（CK）的蛋白质已经成为协调修复与检查点控制的候选者。然而，修复和检查点功能耦合的机制还不太清楚。该项目的目标是了解CK蛋白的修复和检查点功能是如何在细胞中控制的。