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Keifenheim, D.

Publications and source records attributed to Keifenheim, D..

2 recordsLinked to original sources

Size-Dependent Expression of the Fission Yeast Cdc13 Cyclin is Conferred by Translational Regulation

The major fission yeast cyclin, Cdc13, has been shown to increase in concentration in correlation with cell size, and has been proposed to thereby regulate cell size at division. However, the mechanism of its cell-size regulation has been unknown. Here, we show that Cdc13 is regulated post-transcriptionally. Its transcript is not expressed in a size-dependent manner, rather a size-dependent concentration of protein is expressed from a size-independent concentration of mRNA. Moreover, we show that the expression of Cdc13 is, in fact, size dependent, as opposed to simply size-correlated due to time-dependent expression. We identify a 20-amino-acid motif, which includes the APC D-box degron, as necessary and sufficient for size-dependent expression, which allowed us to construct a size-independent allele of cdc13. Using this allele, we show that size-dependent expression of Cdc13 is not required for size control in fission yeast cells.

cell biology↗

The Fission Yeast S-Phase Cyclin Cig2 Can Drive Mitosis

Commitment to mitosis is regulated by cyclin-dependent kinase (CDK) activity. In the fission yeast Schizosaccharomyces pombe, the major B-type cyclin, Cdc13, is necessary and sufficient to drive mitotic entry. Furthermore, Cdc13 is also sufficient to drive S phase, demonstrating that a single cyclin can regulate alternating rounds of replication and mitosis and providing the foundation of the quantitative model of CDK function. It has been assumed that Cig2, a B-type cyclin expressed only during S-phase and incapable of driving mitosis in wild-type cells, was specialized for S-phase regulation. Here, we show that Cig2 is capable of driving mitosis. Cig2/CDK activity drives mitotic catastrophe--lethal mitosis in inviably small cells--in cells that lack CDK inhibition by tyrosine-phosphorylation. Moreover, Cig2/CDK can drive mitosis in the absence of Cdc13/CDK activity and constitutive expression of Cig2 can rescue loss of Cdc13 activity. These results demonstrate that in fission yeast, not only can the presumptive M-phase cyclin drive S phase, but the presumptive S-phase cyclin can drive M phase, further supporting the quantitative model of CDK function. Furthermore, these results provide an explanation, previously proposed on the basis of computational analyses, for the surprising observation that cells expressing a single-chain Cdc13-Cdc2 CDK do not require Y15 phosphorylation for viability. Their viability is due to the fact that in such cells, which lack Cig2/CDK complexes, Cdc13/CDK activity is unable to drive mitotic catastrophe.

cell biology↗