The Francis Crick Institute, London, NW1 1AT UK.
Randall Division of Cell and Molecular Biophysics, King's College, London, SE1 1UL UK.
G3 (Bethesda). 2019 Jul 9;9(7):2183-2194. doi: 10.1534/g3.119.400117.
The yeast centrosome or Spindle Pole Body (SPB) is an organelle situated in the nuclear membrane, where it nucleates spindle microtubules and acts as a signaling hub. Various studies have explored the effects of forcing individual proteins to interact with the yeast SPB, however no systematic study has been performed. We used synthetic physical interactions to detect proteins that inhibit growth when forced to associate with the SPB. We found the SPB to be especially sensitive to relocalization, necessitating a novel data analysis approach. This novel analysis of SPI screening data shows that regions of the cell are locally more sensitive to forced relocalization than previously thought. Furthermore, we found a set of associations that result in elevated SPB number and, in some cases, multi-polar spindles. Since hyper-proliferation of centrosomes is a hallmark of cancer cells, these associations point the way for the use of yeast models in the study of spindle formation and chromosome segregation in cancer.
酵母中心体或纺锤体极体(SPB)是一种位于核膜中的细胞器,在那里它起始纺锤体微管并作为信号枢纽。各种研究都探讨了迫使单个蛋白质与酵母 SPB 相互作用的效果,但尚未进行系统研究。我们使用合成物理相互作用来检测当被迫与 SPB 结合时抑制生长的蛋白质。我们发现 SPB 对重定位特别敏感,需要一种新的数据分析方法。对 SPI 筛选数据的这种新分析表明,与之前的想法相比,细胞的区域对强制重定位的局部敏感性更高。此外,我们发现了一组关联,导致 SPB 数量增加,在某些情况下还导致多极纺锤体。由于中心体的过度增殖是癌细胞的一个标志,这些关联为使用酵母模型研究癌症中的纺锤体形成和染色体分离指明了方向。