The Cdc20 homolog, FZY-1, and its interacting protein, IFY-1, are required for proper chromosome segregation in Caenorhabditis elegans.

Accurate chromosome segregation is achieved by a series of highly regulated processes that culminate in the metaphase-to-anaphase transition of the cell cycle. In the budding yeast Saccharomyces cerevisiae, the degradation of the securin protein Pds1 1, 2, 3 reverses the binding and inhibition of the separase protein Esp1 [4]. Esp1 cleaves Scc1. That cleavage promotes the dissociation of the cohesin complex from the chromosomes 5, 6 and leads the separation of sister chromatids. Proteolysis of Pds1 is regulated by the anaphase-promoting complex (APC), a large multi-subunit E3 ubiquitin ligase [7] whose activity is regulated by Cdc20/Fizzy 8, 9, 10, 11. We have previously shown that the Caenorhabditis elegans genes mdf-1/MAD1 and mdf-2/MAD2 encode key members of the spindle checkpoint [12]. Loss of function of either gene leads to an accumulation of somatic and heritable defects and ultimately results in death. Here we show that a missense mutation in fzy-1/CDC20/Fizzy suppresses mdf-1 lethality. We identified a FZY-1-interacting protein, IFY-1, a novel destruction-box protein. IFY-1 accumulates in one-cell-arrested emb-30/APC4 embryos and interacts with SEP-1, a C. elegans separase, suggesting that IFY-1 functions as a C. elegans securin.