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.
Bibliographical noteFunding Information:
We are grateful to Christiana Baer and the Sanderson Center for Optical Experimentation (SCOpE) for access to, and technical support for, the DeltaVision OMX microscope, Peter Cook for sharing his Freestyle Fluidics technology before publication, to Peter Pryciak and members of the Rhind lab for helpful feedback on the manuscript during its writing, and to Jacky Hayles, Damien Coudreuse, and Matthew Swaffer for insightful comments on the manuscript as a preprint. This work was supported by National Institutes of Health grant GM134300 to NR.
© The Author(s) 2020.
- Cell cycle
- Cyclin-dependent kinase
- Schizosaccharomyces pombe