Role of the central kinetochore in chromosome segregation

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，染色体附着在有丝分裂纺锤体的微管上，第二，作用力将染色体拉向细胞的两极，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相协调。着丝粒是一种复杂的蛋白质结构，与染色体着丝粒有关。虽然着丝粒和着丝粒的结构和组织在真核生物中是不同的，但它们在所有类型的细胞中都扮演着进化上保守的中心角色，将染色体附着到微管上。染色体附着，或双向，是一个容易出错的过程。着丝粒不仅需要分离染色体，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，这是进入后期所必需的。双向缺陷导致纺锤体缺乏张力，并被局部报道；一个染色体上的缺陷足以触发a)有缺陷的连接的修复，如果修复不完整，b)激活细胞周期检查点，推迟进入后期。修复机制和检验点激活对动粒的要求已经很好地建立了。一旦检查点被激活，细胞周期延迟必须保持，直到所有附件都已修复。在过去的几年里，中央动粒蛋白(CK)已经成为协调修复和检查点控制的候选蛋白。然而，修复和检查点功能耦合的机制却鲜为人知。这个项目的目标是了解CK蛋白的修复和检查点功能是如何在细胞中控制的。

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.