Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2010 Nov 12;5(11):e15426. doi: 10.1371/journal.pone.0015426.
The Saccharomyces cerevisiae centrosome or spindle pole body (SPB) is a dynamic structure that is remodeled in a cell cycle dependent manner. The SPB increases in size late in the cell cycle and during most cell cycle arrests and exchanges components during G1/S. We identified proteins involved in the remodeling process using a strain in which SPB remodeling is conditionally induced. This strain was engineered to express a modified SPB component, Spc110, which can be cleaved upon the induction of a protease. Using a synthetic genetic array analysis, we screened for genes required only when Spc110 cleavage is induced. Candidate SPB remodeling factors fell into several functional categories: mitotic regulators, microtubule motors, protein modification enzymes, and nuclear pore proteins. The involvement of candidate genes in SPB assembly was assessed in three ways: by identifying the presence of a synthetic growth defect when combined with an Spc110 assembly defective mutant, quantifying growth of SPBs during metaphase arrest, and comparing distribution of SPB size during asynchronous growth. These secondary screens identified four genes required for SPB remodeling: NUP60, POM152, and NCS2 are required for SPB growth during a mitotic cell cycle arrest, and UBC4 is required to maintain SPB size during the cell cycle. These findings implicate the nuclear pore, urmylation, and ubiquitination in SPB remodeling and represent novel functions for these genes.
酿酒酵母中心体或纺锤体极体(SPB)是一种动态结构,其在细胞周期依赖性方式下进行重塑。SPB 在细胞周期晚期以及大多数细胞周期停滞时增大,并在 G1/S 期间交换组件。我们使用一种条件诱导 SPB 重塑的菌株来鉴定参与重塑过程的蛋白质。该菌株被设计成表达一种经过修饰的 SPB 成分 Spc110,该成分可以在蛋白酶诱导时被切割。使用合成遗传阵列分析,我们筛选了仅在 Spc110 切割诱导时需要的基因。候选 SPB 重塑因子分为几个功能类别:有丝分裂调节剂、微管马达、蛋白质修饰酶和核孔蛋白。候选基因在 SPB 组装中的参与通过三种方式进行评估:当与 Spc110 组装缺陷突变体组合时,通过鉴定是否存在合成生长缺陷,量化有丝分裂期停滞期间 SPB 的生长,以及比较异步生长期间 SPB 大小的分布。这些二次筛选鉴定了四个需要进行 SPB 重塑的基因:NUP60、POM152 和 NCS2 在有丝分裂细胞周期停滞期间需要 SPB 生长,UBC4 在细胞周期期间需要维持 SPB 大小。这些发现表明核孔、urmylation 和泛素化在 SPB 重塑中起作用,并且代表这些基因的新功能。