Haase S B, Winey M, Reed S I
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 94035, USA.
Nat Cell Biol. 2001 Jan;3(1):38-42. doi: 10.1038/35050543.
Organelles called centrosomes in metazoans or spindle pole bodies (SPBs) in yeast direct the assembly of a bipolar spindle that is essential for faithful segregation of chromosomes during mitosis. Abnormal accumulation of multiple centrosomes leads to genome instability, and has been observed in both tumour cells and cells with targeted mutations in tumour-suppressor genes. The defects that lead to centrosome amplification are not understood. We have recapitulated the multiple-centrosome phenotype in budding yeast by disrupting the activity of specific cyclin-dependent kinase (CDK) complexes. Our observations are reminiscent of mechanisms that govern DNA replication, and show that specific cyclin/CDK activities function both to promote SPB duplication and to prevent SPB reduplication.
后生动物中被称为中心体的细胞器或酵母中的纺锤体极体(SPB)指导双极纺锤体的组装,这对于有丝分裂期间染色体的准确分离至关重要。多个中心体的异常积累会导致基因组不稳定,并且在肿瘤细胞和肿瘤抑制基因发生靶向突变的细胞中均已观察到。导致中心体扩增的缺陷尚不清楚。我们通过破坏特定细胞周期蛋白依赖性激酶(CDK)复合物的活性,在芽殖酵母中重现了多中心体表型。我们的观察结果让人联想到控制DNA复制的机制,并表明特定的细胞周期蛋白/CDK活性既起到促进SPB复制的作用,又能防止SPB再次复制。