The centrosome is the primary microtubule-organizing center (MTOC) of most eukaryotic cells and plays an essential role in cell polarity, protein trafficking and the formation of a bipolar mitotic spindle. A pair of centrioles forms the structural core of the centrosome. The centriole pair must duplicate once and only once per cell cycle to ensure a bipolar mitotic spindle and proper chromosome segregation. Many human cancer cells have excess centrosomes, which presumably exacerbates the chromosomal aberrations that occur in tumors. Thus, a better understanding of the centrosome and how it duplicates could help to shed light on the mechanisms of how cells become cancerous. The kinase ZYG-1 is essential for centrosome duplication in C.elegans and functions by recruiting a series of proteins to assemble a new centriole adjacent to the parent one. However, in embryos that lack ZYG-1 activity, this fails to occur, resulting in the assembly of monopolar spindles at the two-cell stage and embryonic lethality. To understand how ZYG-1 activity is regulated, I have been studying the
szy-5 (suppressor of
zyg-1) gene. The szy-5Italic Text
(bs7Italic Text) mutation rescues the lethality and spindle defect observed in zyg-1Italic Text
(it25Italic Text) embryos. Interestingly, the szy-5Italic Text
(bs7Italic Text) mutation also causes a temperature-sensitive embryonic lethal phenotype of its own. These embryos display cell division defects such as a delayed cell cycle and mis-positioning of the mitotic spindle. Also, novel aggregates frequently form within the cytoplasm of szy-5Italic Text
(bs7Italic Text) embryos. We have found that the szy-5Italic Text gene encodes a zinc finger protein, and exhibits cytoplasmic and nuclear localization. An inItalic Text vitroItalic Text assay suggests that SZY-5 can bind RNA. Quantitative, real-time PCR analysis does not show any significant differences between wild-type and the szy-5Italic Text
(bs7Italic Text) mutant in the levels of mRNAs that encode centrosomal proteins. However, in contrast to the wild type, szy-5Italic Text
(bs7Italic Text) embryos exhibit increased levels of GFP-gg-tubulin at the centrosome. Preliminary results suggest that the levels of the SPD-2 protein may also be increased at centrosome in szy-5Italic Text
(bs7Italic Text) embryos. Our results suggest a model in which SZY-5 functions post-transcriptionally to regulate the level of proteins at the centrosome.