Degradation of the Mitotic Cyclin Clb3 Is not Required for Mitotic Exit but Is Necessary for G1 Cyclin Control of the Succeeding Cell Cycle

Abstract

B-type cyclins promote mitotic entry and inhibit mitotic exit. In Saccharomyces cerevisiae, four B-type cyclins, Clb1-4, carry out essential mitotic roles, with substantial but incomplete overlap of function among them. Previous work in many organisms has indicated that B-type cyclin-dependent inhibition of mitotic exit imposes a requirement for mitotic destruction of B-type cyclins. For instance, precise genomic removal of the Clb2 destruction box (D box) prevents mitotic proteolysis of Clb2, and blocks mitotic exit. Here, we show that, despite significant functional overlap between Clb2 and Clb3, D-box-dependent Clb3 proteolysis is completely dispensable for mitotic exit. Removal of the Clb3 D box results in abundant Clb3 protein and associated kinase throughout the cell cycle, but mitotic exit occurs with close to normal timing. Clb3 degradation is required for pre-Start G 1 control in the succeeding cell cycle. Deleting the CLB3 D box essentially eliminates all time delay before cell cycle Start following division, even in very small newborn cells. CLB3Ddb cells show no cell cycle arrest response to mating pheromone, and CLB3Ddb completely bypasses the requirement for CLN G 1 cyclins, even in the absence of the early expressed B-type cyclins CLB5,6. Thus, regulated mitotic proteolysis of Clb3 is specifically required to make passage of Start in the succeeding cell cycle "memoryless"-dependent on conditions within that cycle, and independent of events such as B-type cyclin accumulation that occurred in the preceding cycle.

Proline-Rich Motifs Control G2-CDK Target Phosphorylation and Priming an Anchoring Protein for Polo Kinase Localization

“…The common specificity could mediate the universal functions of Clb cyclins, such as triggering DNA replication (Donaldson et al, 1998), but the cyclin-specific motifs could allow greater temporal control of phosphorylation events, as there are differences in functions of even closely related cyclins. For example, Clb3 promotes timely spindle assembly, but is incapable of substituting Clb2 in triggering anaphase or inhibiting mitotic exit (Pecani and Cross, 2016;Richardson et al, 1992).…”

Cyclin-Specific Docking Mechanisms Reveal the Complexity of M-CDK Function in the Cell Cycle

“…Additionally, only mitotic Cdk1 complexes are subjected to inhibitory phosphorylation by Swe1 (Hu and Aparicio, 2005, Keaton et al., 2007). Also, degradation of Clb2 (mitotic CDK [M-CDK]) is essential for mitotic exit whereas degradation of Clb5 (S-CDK) and Clb3 (G2-CDK) is not, indicating that only M-CDK inhibits mitotic exit (Wäsch and Cross, 2002, Pecani and Cross, 2016). Until now, there has been no reported evidence of specific docking mechanisms for M-CDK.…”

Control of division and microtubule dynamics in Chlamydomonas by cyclin B/CDKB1 and the anaphase-promoting complex

“…In yeast and animals, cyclin B degradation is essential for completion of cytokinesis and for initiation of a new round of DNA replication (Murray & Kirschner, 1989; Wäsch & Cross, 2002). In yeast, this requirement for cyclin B degradation is specific to the Clb2 B-type cyclin; mitotic exit proceeds even without the destruction of another B-type cyclin, Clb3, and the degradation of Clb3 is not essential for viability (Pecani & Cross, 2016). In Nicotiana tabacum , expression of non-degradable CYCB1 leads to endomitosis with failed cytokinesis (Weingartner et al, 2004).…”