How is the Spindle Assembly Checkpoint turned off?

如何关闭主轴装配检查点？

• 批准号: BB/I022376/1
• 负责人: Jonathon Pines
• 金额: $ 37.37万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI022376%2F1
• 关键词: How; Spindle; Assembly; Checkpoint; turned

When a cell divides it is essential that the two daughter cells inherit an equal and identical copy of the chromosomes. When this goes wrong it can be lethal for the cell, or even lead to cancer. To prevent such errors the cell is able to stop and wait in the middle of dividing if it detects that any of its chromosomes are not being pulled to the middle of the cell by a machine called the mitotic spindle. It is only when all the chromosomes are properly attached to the spindle that the cell goes on to divide its chromosomes. We are investigating this process and in particular the mechanism that links how the cell detects whether chromosomes are attached to the spindle to the engine that drives cells through mitosis. We would like work out how the 'brake' on the engine is removed when all the chromosomes are attached. This mechanism is the target of a number of anti-cancer drugs, therefore, a better understanding of how this mechanism works should help to design better drugs with fewer side-effects.

当一个细胞分裂时，两个子细胞继承一个相等和相同的染色体拷贝是至关重要的。当这个过程出错时，它可能对细胞是致命的，甚至导致癌症。为了防止这样的错误，如果细胞检测到它的任何染色体没有被称为有丝分裂纺锤体的机器拉到细胞中间，它就能够在分裂过程中停止并等待。只有当所有的染色体都正确地附着在纺锤体上时，细胞才能继续分裂染色体。我们正在研究这一过程，特别是将细胞如何检测染色体是否附着在纺锤体上与驱动细胞进行有丝分裂的引擎联系起来的机制。我们想弄清楚当所有染色体都连接在一起时，发动机上的“刹车”是如何被移除的。这一机制是许多抗癌药物的靶点，因此，更好地了解这一机制的工作原理将有助于设计更好的药物，减少副作用。

项目成果

The spindle assembly checkpoint works like a rheostat rather than a toggle switch.

• DOI: 10.1038/ncb2855
• 发表时间: 2013-11
• 期刊: Nature cell biology
• 影响因子: 21.3