The fission yeast S-phase cyclin Cig2 can drive mitosis

Pickering, Mary T.; Magner, Mira; Keifenheim, Daniel; Rhind, Nick

doi:10.1093/genetics/iyaa002

Cited by 3 publications

(3 citation statements)

References 56 publications

(85 reference statements)

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“…It has been well established that Cdc13–Cdk1 (the fission yeast M-CDK) can compensate for loss of Cig2–Cdk1 (the fission yeast S-CDK) 9 , but it is not clear whether S-CDK can compensate for M-CDK. Early studies using a temperature-sensitive cdc13 mutant showed that Cig2–Cdk1 could initiate but not complete mitosis 17 , 18 , although a more recent study using the temperature-sensitive cdc13-G282D strain has suggested that Cig2–Cdk1 can completely compensate for Cdc13–Cdk1 loss 22 . However, the authors of this study cautioned that this temperature-sensitive mutant might not have eliminated all M-CDK activity from the cell, a potential problem because they reported that cdc13-G282D cells accumulated dividing septated cells at their restrictive temperature, indicating that mitoses were indeed taking place.…”

Section: S-cdk Cannot Complete Mitosismentioning

confidence: 99%

Core control principles of the eukaryotic cell cycle

Basu

Greenwood

Jones

et al. 2022

Nature

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Cyclin-dependent kinases (CDKs) lie at the heart of eukaryotic cell cycle control, with different cyclin–CDK complexes initiating DNA replication (S-CDKs) and mitosis (M-CDKs)1,2. However, the principles on which cyclin–CDK complexes organize the temporal order of cell cycle events are contentious3. One model proposes that S-CDKs and M-CDKs are functionally specialized, with substantially different substrate specificities to execute different cell cycle events4–6. A second model proposes that S-CDKs and M-CDKs are redundant with each other, with both acting as sources of overall CDK activity7,8. In this model, increasing CDK activity, rather than CDK substrate specificity, orders cell cycle events9,10. Here we reconcile these two views of core cell cycle control. Using phosphoproteomic assays of in vivo CDK activity in fission yeast, we find that S-CDK and M-CDK substrate specificities are remarkably similar, showing that S-CDKs and M-CDKs are not completely specialized for S phase and mitosis alone. Normally, S-CDK cannot drive mitosis but can do so when protein phosphatase 1 is removed from the centrosome. Thus, increasing S-CDK activity in vivo is sufficient to overcome substrate specificity differences between S-CDK and M-CDK, and allows S-CDK to carry out M-CDK function. Therefore, we unite the two opposing views of cell cycle control, showing that the core cell cycle engine is largely based on a quantitative increase in CDK activity through the cell cycle, combined with minor and surmountable qualitative differences in catalytic specialization of S-CDKs and M-CDKs.

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Section: S-cdk Cannot Complete Mitosismentioning

confidence: 99%

Core control principles of the eukaryotic cell cycle

Basu

Greenwood

Jones

et al. 2022

Nature

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“…Thus, these results suggest that there are only quantitative differences in the ability of different CDKs to the control, S-phase, or mitosis. This principle is conserved in fission yeast, where the S-phase CDK-cyclin complex can trigger mitosis [99,100].…”

Section: Specific Cdk-cyclin Complexes Are Not Essential For Entry In...mentioning

confidence: 99%

Explaining Redundancy in CDK-Mediated Control of the Cell Cycle: Unifying the Continuum and Quantitative Models

Fisher

Krasińska

2022

Cells

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In eukaryotes, cyclin-dependent kinases (CDKs) are required for the onset of DNA replication and mitosis, and distinct CDK–cyclin complexes are activated sequentially throughout the cell cycle. It is widely thought that specific complexes are required to traverse a point of commitment to the cell cycle in G1, and to promote S-phase and mitosis, respectively. Thus, according to a popular model that has dominated the field for decades, the inherent specificity of distinct CDK–cyclin complexes for different substrates at each phase of the cell cycle generates the correct order and timing of events. However, the results from the knockouts of genes encoding cyclins and CDKs do not support this model. An alternative “quantitative” model, validated by much recent work, suggests that it is the overall level of CDK activity (with the opposing input of phosphatases) that determines the timing and order of S-phase and mitosis. We take this model further by suggesting that the subdivision of the cell cycle into discrete phases (G0, G1, S, G2, and M) is outdated and problematic. Instead, we revive the “continuum” model of the cell cycle and propose that a combination with the quantitative model better defines a conceptual framework for understanding cell cycle control.

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“…It has been well established that Cdc13-Cdk1 (M-CDK) can compensate for Cig2-Cdk1 (S-CDK) 7 , but it is not clear if S-CDK can compensate for M-CDK. Early studies using a temperature sensitive cdc13 mutant showed that Cig2-Cdk1 could initiate mitosis could not complete it 17,18 , although a more recent study using the temperature sensitive cdc13-G282D, has suggested that Cig2-Cdk1 can completely compensate for Cdc13-Cdk1 22 . However, the authors of this study cautioned that this temperature sensitive mutant might not have eliminated all the M-CDK activity from the cell, a potential problem because they reported cdc13-G282D cells accumulated dividing septated cells at their restrictive temperature, suggesting that mitoses were taking place.…”

Section: S-cdk Can Initiate Mitosis But Not Complete Itmentioning

confidence: 99%

Core Control Principles of the Eukaryotic Cell Cycle

Basu

Nurse

Jones

2021

Preprint

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Cyclin dependent kinases (CDKs) lie at the heart of eukaryotic cell cycle control, with different Cyclin-CDK complexes initiating DNA replication (S-CDKs) and mitosis (M-CDKs). However, the principles on which Cyclin-CDKs organise the temporal order of cell cycle events are contentious. The currently most widely accepted model, is that the S-CDKs and M-CDKs are functionally specialised, with significant different substrate specificities to execute different cell cycle events. A second model is that S-CDKs and M-CDKs are redundant with each other, with both acting as sources of overall cellular CDK activity. Here we reconcile these two views of core cell cycle control. Using a multiplexed phosphoproteomics assay of in vivo S-CDK and M-CDK activities in fission yeast, we show that S-CDK and M-CDK substrate specificities are very similar, showing that S-CDKs are not completely specialised for S-phase alone. Normally S-CDK cannot undergo mitosis, but is able to do so when Protein Phosphatase 1 (PP1) is removed from the centrosome, allowing several mitotic substrates to be better phosphorylated by S-CDK in vivo. Thus, an increase in S-CDK activity in vivo is sufficient to allow S-CDK to carry out M-CDK function. Therefore, we unite the two opposing views of cell cycle control, showing that the core cell cycle engine which temporally orders cell cycle progression is largely based upon a quantitative increase of CDK activity through the cell cycle, combined with minor qualitative differences in catalytic specialisation of S-CDKs and M-CDKs.

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The fission yeast S-phase cyclin Cig2 can drive mitosis

Cited by 3 publications

References 56 publications

Core control principles of the eukaryotic cell cycle

Core control principles of the eukaryotic cell cycle

Explaining Redundancy in CDK-Mediated Control of the Cell Cycle: Unifying the Continuum and Quantitative Models

Core Control Principles of the Eukaryotic Cell Cycle

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