Kemp Catherine A, Song Mi Hye, Addepalli Murali Krishna, Hunter Ginger, O'Connell Kevin
Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Genetics. 2007 May;176(1):95-113. doi: 10.1534/genetics.107.071803. Epub 2007 Apr 19.
In Caenorhabditis elegans, the kinase ZYG-1 is required for centrosome duplication. To identify factors that interact with ZYG-1, we used a classical genetic approach and identified 21 szy (suppressor of zyg-1) genes that when mutated restore partial viability to a zyg-1 mutant. None of the suppressors render animals completely independent of zyg-1 activity and analysis of a subset of the suppressors indicates that all restore the normal process of centrosome duplication to zyg-1 mutants. Thirteen of these suppressor mutations confer phenotypes of their own and cytological examination reveals that these genes function in a variety of cellular processes including cell cycle timing, microtubule organization, cytokinesis, chromosome segregation, and centrosome morphology. Interestingly, several of the szy genes play a role in attaching the centrosome to the nuclear envelope. We have found that one such szy gene is sun-1, a gene encoding a nuclear envelope component. We further show that the role of SUN-1 in centrosome duplication is distinct from its role in attachment. Our approach has thus identified numerous candidate regulators of centrosome duplication and uncovered an unanticipated regulatory mechanism involving factors that tether the centrosome to the nucleus.
在秀丽隐杆线虫中,激酶ZYG-1是中心体复制所必需的。为了鉴定与ZYG-1相互作用的因子,我们采用了经典的遗传学方法,鉴定出21个szy(zyg-1的抑制因子)基因,这些基因发生突变后能使zyg-1突变体恢复部分活力。没有一个抑制因子能使动物完全不依赖zyg-1的活性,对一部分抑制因子的分析表明,所有这些抑制因子都能使zyg-1突变体恢复正常的中心体复制过程。其中13个抑制因子突变具有自身的表型,细胞学检查显示这些基因在多种细胞过程中发挥作用,包括细胞周期定时、微管组织、胞质分裂、染色体分离和中心体形态。有趣的是,几个szy基因在将中心体附着到核膜上起作用。我们发现其中一个这样的szy基因是sun-1,它是一个编码核膜成分的基因。我们进一步表明,SUN-1在中心体复制中的作用与其在附着中的作用不同。因此,我们的方法鉴定出了众多中心体复制的候选调节因子,并揭示了一种意想不到的调节机制,该机制涉及将中心体与细胞核相连的因子。