Muhua L, Adames N R, Murphy M D, Shields C R, Cooper J A
Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Nature. 1998 Jun 4;393(6684):487-91. doi: 10.1038/31014.
Checkpoint controls ensure that events of the cell-division cycle are completed with fidelity and in the correct order. In budding yeast with a mutation in the motor protein dynein, the mitotic spindle is often misaligned and therefore slow to enter the neck between mother cell and budding daughter cell. When this occurs, cytokinesis (division of the cytoplasm into two) is delayed until the spindle is properly positioned. Here we describe mutations that abolish this delay, indicating the existence of a new checkpoint mechanism. One mutation lies in the gene encoding the yeast homologue of EB1, a human protein that binds the adenomatous polyposis coli (APC) protein, a tumour suppressor. EB1 is located on microtubules of the mitotic spindle and is important in spindle assembly. EB1 may therefore, by associating with microtubules, contribute to the sensor mechanism that activates the checkpoint. Another mutation affects Stt4, a phosphatidylinositol-4-OH kinase. Cold temperature is an environmental stimulus that causes misalignment of the mitotic spindle in yeast and appears to activate this checkpoint mechanism.
关卡控制确保细胞分裂周期中的事件能够准确无误且按正确顺序完成。在动力蛋白驱动蛋白发生突变的芽殖酵母中，有丝分裂纺锤体常常排列错误，因此进入母细胞和出芽子细胞之间颈部的速度很慢。当这种情况发生时，胞质分裂（细胞质分裂为两部分）会延迟，直到纺锤体正确定位。在这里，我们描述了消除这种延迟的突变，这表明存在一种新的关卡机制。其中一个突变位于编码酵母EB1同源物的基因中，EB1是一种人类蛋白，可与肿瘤抑制蛋白腺瘤性息肉病大肠杆菌（APC）蛋白结合。EB1位于有丝分裂纺锤体的微管上，对纺锤体组装很重要。因此，EB1可能通过与微管结合，参与激活关卡的传感机制。另一个突变影响Stt4，一种磷脂酰肌醇-4-OH激酶。低温是一种环境刺激因素，会导致酵母中有丝分裂纺锤体排列错误，并且似乎会激活这种关卡机制。
