Simmons Kovacs Laura A, Nelson Christine L, Haase Steven B
Department of Biology, Duke University, Durham, NC 27708-0338, USa.
Mol Biol Cell. 2008 Aug;19(8):3243-53. doi: 10.1091/mbc.e08-02-0148. Epub 2008 May 14.
Centrosome duplication must be tightly controlled so that duplication occurs only once each cell cycle. Accumulation of multiple centrosomes can result in the assembly of a multipolar spindle and lead to chromosome mis-segregation and genomic instability. In metazoans, a centrosome-intrinsic mechanism prevents reduplication until centriole disengagement. Mitotic cyclin/cyclin-dependent kinases (CDKs) prevent reduplication of the budding yeast centrosome, called a spindle pole body (SPB), in late S-phase and G2/M, but the mechanism remains unclear. How SPB reduplication is prevented early in the cell cycle is also not understood. Here we show that, similar to metazoans, an SPB-intrinsic mechanism prevents reduplication early in the cell cycle. We also show that mitotic cyclins can inhibit SPB duplication when expressed before satellite assembly in early G1, but not later in G1, after the satellite had assembled. Moreover, electron microscopy revealed that SPBs do not assemble a satellite in cells expressing Clb2 in early G1. Finally, we demonstrate that Clb2 must localize to the cytoplasm in order to inhibit SPB duplication, suggesting the possibility for direct CDK inhibition of satellite components. These two mechanisms, intrinsic and extrinsic control by CDK, evoke two-step system that prevents SPB reduplication throughout the cell cycle.
中心体复制必须受到严格控制,以便每个细胞周期仅发生一次复制。多个中心体的积累会导致多极纺锤体的组装,并导致染色体错分离和基因组不稳定。在多细胞动物中,一种中心体内在机制可防止在中心粒脱离之前进行再复制。有丝分裂周期蛋白/周期蛋白依赖性激酶(CDK)在S期后期和G2/M期可防止芽殖酵母中心体(称为纺锤体极体,SPB)的再复制,但其机制尚不清楚。细胞周期早期如何防止SPB再复制也不清楚。在这里,我们表明,与多细胞动物类似,一种SPB内在机制在细胞周期早期防止再复制。我们还表明,当有丝分裂周期蛋白在G1早期卫星组装之前而非之后表达时,可抑制SPB复制。此外,电子显微镜显示,在G1早期表达Clb2的细胞中,SPB不会组装卫星。最后,我们证明Clb2必须定位于细胞质才能抑制SPB复制,这表明CDK可能直接抑制卫星成分。这两种机制,即CDK的内在和外在控制,引发了一个两步系统,可在整个细胞周期中防止SPB再复制。