EXIT FROM MITOSIS IS REGULATED BY DROSOPHILA FIZZY AND THE SEQUENTIALDESTRUCTION OF CYCLIN-A, CYCLIN-B AND CYCLIN-B3

While entry into mitosis is triggered by activation of cdc2 kinase, ex it from mitosis requires inactivation of this kinase. Inactivation res ults from proteolytic degradation of the regulatory cyclin subunits du ring mitosis. At least three different cyclin types, cyclins A, B and B3, associate with cdc2 kinase in higher eukaryotes and are sequential ly degraded in mitosis. We show here that mutations in the Drosophila gene fizzy (fzy) block the mitotic degradation of these cyclins. Moreo ver, expression of mutant cyclins (Delta cyclins) lacking the destruct ion box motif required for mitotic degradation affects mitotic progres sion at distinct stages, Delta cyclin A results in a delay in metaphas e, Delta cyclin B in an early anaphase arrest and Delta cyclin B3 in a late anaphase arrest, suggesting that mitotic progression beyond meta phase is ordered by the sequential degradation of these different cycl ins, Coexpression of Delta cyclins A, B and B3 allows a delayed separa tion of sister chromosomes, but interferes with chromosome segregation to the poles. Mutations in fzy block both sister chromosome separatio n and segregation, indicating that fzy plays a crucial role in the met aphase/anaphase transition.