THE DROSOPHILA CELL-CYCLE GENE FIZZY IS REQUIRED FOR NORMAL DEGRADATION OF CYCLIN-A AND CYCLIN-B DURING MITOSIS AND HAS HOMOLOGY TO THE CDC20 GENE OF SACCHAROMYCES-CEREVISIAE

The Drosophila cell cycle gene fizzy (fzy) is required for normal execution of the metaphase-anaphase transition. We have cloned fzy, and confirmed this by P-element mediated germline transformation rescue. Sequence analysis predicts that fzy encodes a protein of 526 amino acids, the carboxy half of which has significant homology to the Saccharomyces cerevisiae cell cycle gene CDC20. A monoclonal antibody against fly detects a single protein of the expected size, 59 kD, in embryonic extracts. In early embryos fly is expressed in all proliferating tissues; in late embryos fly expression declines in a tissue-specific manner correlated with cessation of cell division. During interphase fly protein is present in the cytoplasm; while in mitosis fly becomes ubiquitously distributed throughout the cell except for the area occupied by the chromosomes. The metaphase arrest phenotype caused by fzy mutations is associated with failure to degrade both mitotic cyclins A and B, and an enrichment of spindle microtubules at the expense of astral microtubules. Our data suggest that fly function is required for normal cell cycle-regulated proteolysis that is necessary for successful progress through mitosis.