Punctuated Cyclin Synthesis Drives Early Embryonic Cell Cycle Oscillations

Cyclin B activates cyclin-dependent kinase 1 (CDK1) at mitosis, but conflicting views have emerged on the dynamics of its synthesis during embryonic cycles, ranging from continous translation to rapid synthesis during mitosis. Here we show that a CDK1-mediated negative-feedback loop attenuates cyclin production before mitosis. We employed Xenopus early embryonic cycling extracts as our model system and applied biochemical assays to study the translation of cyclin B on both protein and mRNA levels. Cyclin B plateaus before peak CDK1 activation, and proteasome inhibition caused minimal accumulation during mitosis. Inhibiting CDK1 permitted continual cyclin B synthesis, whereas adding non-degradable cyclin stalled it. Cycloheximide treatment before mitosis affected neither cyclin levels nor mitotic entry, corroborating this repression. Attenuated cyclin production collaborates with its destruction, since excess cyclin B1 mRNA accelerated cyclin synthesis and caused incomplete proteolysis and mitotic arrest. This repression involved neither adenylation nor the 3’ UTR, but it corresponded with a shift in cyclin B1 mRNA from polysome to non-polysome fractions. A pulse-driven CDK1-(anaphase promoting complex) APC model corroborated these results, revealing reduced cyclin levels during an oscillation and permitting more effective removal. This design also increased the robustness of the oscillator, with lessened sensitivity to changes in cyclin synthesis rate. Altogether, this study underscores that attenuating cyclin synthesis late in interphase improves both the efficiency and robustness of the CDK1-APC oscillator.