The functions of the cullin-2-ZYG-11 complex in promoting meiosis and anterior-posterior polarity in C. elegans
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Chromosome segregation is one of the most important events in the life cycle of a cell. Unequal segregation of chromosomes is the cause of a number of disorders in humans and other organisms. In this study we demonstrate that in Caenorhabditis elegans, the ubiquitin ligase CUL-2 is required for chromosome segregation during meiosis. In cul-2 mutant zygotes, the maternal chromosomes fail to complete the second meiotic division. Inspection of chromosome and spindle dynamics has revealed that in cul-2 zygotes the meiotic apparatus spends an extended amount of time in the metaphase configuration and fails to proceed towards anaphase. During the metaphase II arrest, premature establishment of anterior-posterior polarity and cytoskeletal defects are observed in the zygote. A second gene, zyg-11, has similar meiosis defects as cul-2. In this report we demonstrate that ZYG-11 serves as a substrate recognition subunit for the CUL-2 ubiquitin ligase. Here we find that ZYG-11 interacts with the CUL-2 complex adaptor Elongin C through a nematode specific VHL box motif. ZYG-11 homologs in C. elegans and humans also function as substrate recognition subunits of CUL-2. ZYG-11 To identify the substrates of the CUL-2 complex we have undertaken a zyg-11 suppressor screen. We anticipate that this screen will identify novel cell cycle regulators that will explain the complex phenotypes observed in cul-2 and zyg-11 mutants.