The schedule of destruction of three mitotic cyclins can dictate the timing of events during exit from mitosis

Background: Degradation of the mitotic cyclins is a hallmark of the exit fr om mitosis, Induction of stable versions of each of the three mitotic cycli ns of Drosophila, cyclins A, B, and B3, arrests mitosis with different phen otypes. We tested a recent proposal that the destruction of the different c yclins guides progress through mitosis. Results: Real-time imaging revealed that arrest phenotypes differ because e ach stable cyclin affects specific mitotic events differently. Stable cycli n A prolonged or blocked chromosome disjunction, leading to metaphase arres t. Stable cyclin B allowed the transition to anaphase, but anaphase A chrom osome movements were slowed, anaphase B spindle elongation did not occur, a nd the monooriented disjoined chromosomes began to oscillate between the sp indle poles. Stable cyclin B3 prevented normal spindle maturation and block ed major mitotic exit events such as chromosome decondensation but nonethel ess allowed chromosome disjunction, anaphase B, and formation of a cytokine tic furrow, which split the spindle. Conclusions: We conclude that degradation of distinct mitotic cyclins is re quired to transit specific steps of mitosis: cyclin A degradation facilitat es chromosome disjunction, cyclin B destruction is required for anaphase B and cytokinesis and for directional stability of univalent chromosome movem ents, and cyclin B3 degradation is required for proper spindle reorganizati on and restoration of the interphase nucleus. We suggest that the schedule of degradation of cyclin A, cyclin B, and then cyclin B3 contributes to the temporal coordination of mitotic events.