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

摘要

B-type cyclins promote mitotic entry and inhibit mitotic exit. In Saccharomyces cerevisiae , four B-type cyclins, [Clb1][1]–[4][2], 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][3] destruction box (D box) prevents mitotic proteolysis of [Clb2][3], and blocks mitotic exit. Here, we show that, despite significant functional overlap between [Clb2][3] and [Clb3][4], D-box-dependent [Clb3][4] proteolysis is completely dispensable for mitotic exit. Removal of the [Clb3][4] D box results in abundant [Clb3][4] protein and associated kinase throughout the cell cycle, but mitotic exit occurs with close to normal timing. [Clb3][4] degradation is required for pre-Start G1 control in the succeeding cell cycle. Deleting the [CLB3][4] D box essentially eliminates all time delay before cell cycle Start following division, even in very small newborn cells. [CLB3][4] ? db cells show no cell cycle arrest response to mating pheromone, and [CLB3][4] ? db completely bypasses the requirement for CLN G1 cyclins, even in the absence of the early expressed B-type cyclins [CLB5][5],[6][6] . Thus, regulated mitotic proteolysis of [Clb3][4] 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. [1]: http://www.yeastgenome.org/locus/S000003340/overview [2]: http://www.yeastgenome.org/locus/S000004200/overview [3]: http://www.yeastgenome.org/locus/S000006323/overview [4]: http://www.yeastgenome.org/locus/S000002314/overview [5]: http://www.yeastgenome.org/locus/S000006324/overview [6]: http://www.yeastgenome.org/locus/S000003341/overview