Separase is required for chromosome segregation during meiosis I in Caenorhabditis elegans

Background: Chromosome segregation during mitosis and meiosis is triggered by dissolution of sister chromatid cohesion, which is mediated by the cohes in complex. Mitotic sister chromatid disjunction requires that cohesion be lost along the entire length of chromosomes, whereas homolog segregation at meiosis I only requires loss of cohesion along chromosome arms. During ani mal cell mitosis, cohesin is lost in two steps. A nonproteolytic mechanism removes cohesin along chromosome arms during prophase, while the proteolyti c cleavage of cohesin's Scc1 subunit by separase removes centromeric cohesi n at anaphase. In Saccharomyces cerevisiae and Caenorhabditis elegans, meio tic sister chromatid cohesion is mediated by Rec8, a meiosis-specific varia nt of cohesin's Scc1 subunit. Homolog segregation in S. cerevisiae is trigg ered by separase-mediated cleavage of Rec8 along chromosome arms. In princi ple, chiasmata could be resolved proteolytically by separase or nonproteoly tically using a mechanism similar to the mitotic "prophase pathway." Results: Inactivation of separase in C. elegans has little or no effect on homolog alignment on the meiosis I spindle but prevents their timely disjun ction. It also interferes with chromatid separation during subsequent embry onic mitotic divisions but does not directly affect cytokinesis. Surprising ly, separase inactivation also causes osmosensitive embryos, possibly due t o a defect in the extraembryonic structures, referred to as the "eggshell." Conclusions: Separase is essential for homologous chromosome disjunction du ring meiosis I. Proteolytic cleavage, presumably of Rec8, might be a common trigger for the first meiotic division in eukaryotic cells. Cleavage of pr oteins other than REC-8 might be necessary to render the eggshell impermeab le to solutes.