Separation of sister chromatids at the metaphase-to-anaphase transition is crucial for accurate chromosome transmission during both meiosis and mitosis. Separase, a CD clan cysteine protease, mediates this separation. Separase cleaves SCC-1, a member of the cohesion complex that holds sister chromatids together, allowing chromosomes to separate and to be drawn towards the poles of the spindle. Caspases also belong to the CD clan of the cysteine protease family and have been shown to cleave SCC1/RAD21 during apoptosis in mammalian cells. We found that the C. elegans caspase CED-3, which has been known strictly from its role in activating programmed cell death, may perform a separase-like function during meiosis I in the hermaphrodite germline and in subsequent embryonic mitotic divisions. To investigate the interplay between apoptosis and other essential cellular processes, we performed an RNAi screen for lethal mutants that are suppressed by a mutation in the pro-apoptotic regulator
ced-4(-). We found that debilitating the function of C. elegans separase
sep-1 by RNAi leads to diminished lethality in a
ced-4(-) background compared to N2. In contrast, we were surprised to find that the lethality of
sep-1(RNAi) is significantly enhanced by mutations in
ced-3. In addition,
ced-3(
n717) enhances X chromosome non-disjunction of
sep-1(RNAi) animals (evident by a Him phenotype), suggesting a role for CED-3 in meiotic chromosome segregation. We visualized chromosome segregation during meiosis and subsequent embryonic mitotic divisions with an H2B::GFP marker. Time-lapse revealed a more severe defect in chromosome segregation in
ced-3(
n717);
sep-1(RNAi) embryos compared to
sep-1(RNAi) embryos. Further, our preliminary observations indicate that while maternal and paternal chromosomes congress to an apparently normal metaphase plate in
sep-1(RNAi) embryos, no metaphase plate forms in
ced-3(
n717);
sep-1(RNAi) embryos, revealing a further role for CED-3 in promoting metaphase plate formation. Analysis of several different
ced-3 alleles suggest that the pro-apoptotic function of CED-3 is separable from its action in chromosome segregation. We conclude that the CED-3 caspase may be capable of performing a separase-like role in chromosome segregation during meiosis I and is involved in metaphase plate formation in early embryos. Since both caspases and separases belong to the CD clan of the cysteine protease family, our findings further suggest that the components of chromosome segregation pathway may have been co-opted by the cell death machinery during the course of evolution.