Mitotic degradation of cyclin A is mediated by multiple and novel destruction signals

Exit from mitosis requires Cdk1 inactivation, with the most prominent mecha nism of Cdk1 inactivation being proteolysis of mitotic cyclins [1]. In high er eukaryotes this involves sequential destruction of A- and B-type cyclins . CycA is destroyed first, and CycA/Cdk1 inactivation is required for the m etaphase-to-anaphase transition [2]. The degradation of CycA is delayed in response to DNA damage but is not prevented when the spindle checkpoint is activated [3, 4]. Cyclin destruction is thought to be mediated by a conserv ed motif, the destruction box (D box). Like B-type cyclins, A-type cyclins contain putative destruction box sequences in their N termini [5] However, no detailed in vivo analysis of the sequence requirements for CycA destruct ion has been described so far. Here we tested several mutations in the CycA coding region for destruction in Drosophila embryos. We show that D box se quences are not essential for mitotic destruction of CycA. Destruction is m ediated by at least three different elements that act in an overlapping fas hion to mediate its mitotic degradation.