FRET-Based Sorting of Live Cells Reveals Shifted Balance between PLK1 and CDK1 Activities During Checkpoint Recovery

Lafranchi, Lorenzo; Müllers, Erik; Rutishauser, Dorothea; Lindqvist, Arne

doi:10.3390/cells9092126

Cited by 4 publications

(2 citation statements)

References 41 publications

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“…By implementing DNA damage in G2 via manipulation of the Cdk1 activation threshold, we found that cells enter M phase with higher CycB-Cdk1 levels after DNA damage in G2 phase. This is in line with recently published experimental results [ 95 ]. Whether the subsequent M phase takes longer than in unperturbed cells, as is predicted by the model, was not assessed in the cited study.…”

Section: Discussionsupporting

confidence: 94%

A modular approach for modeling the cell cycle based on functional response curves

2021

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Modeling biochemical reactions by means of differential equations often results in systems with a large number of variables and parameters. As this might complicate the interpretation and generalization of the obtained results, it is often desirable to reduce the complexity of the model. One way to accomplish this is by replacing the detailed reaction mechanisms of certain modules in the model by a mathematical expression that qualitatively describes the dynamical behavior of these modules. Such an approach has been widely adopted for ultrasensitive responses, for which underlying reaction mechanisms are often replaced by a single Hill function. Also time delays are usually accounted for by using an explicit delay in delay differential equations. In contrast, however, S-shaped response curves, which by definition have multiple output values for certain input values and are often encountered in bistable systems, are not easily modeled in such an explicit way. Here, we extend the classical Hill function into a mathematical expression that can be used to describe both ultrasensitive and S-shaped responses. We show how three ubiquitous modules (ultrasensitive responses, S-shaped responses and time delays) can be combined in different configurations and explore the dynamics of these systems. As an example, we apply our strategy to set up a model of the cell cycle consisting of multiple bistable switches, which can incorporate events such as DNA damage and coupling to the circadian clock in a phenomenological way.

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Section: Discussionsupporting

confidence: 94%

A modular approach for modeling the cell cycle based on functional response curves

2021

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“…By implementing DNA damage in G2 via manipulation of the Cdk1 activation threshold, we found that cells enter M-phase with higher CycB-Cdk1 levels after DNA damage in G2 phase. This is in line with recently published experimental results [88]. Whether the subsequent M-phase takes longer than in unperturbed cells, as is predicted by the model, was not assessed in the cited study.…”

Section: Discussionsupporting

confidence: 83%

A modular approach for modeling the cell cycle based on functional response curves

Boeck

Rombouts

Gelens

2021

Preprint

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Modeling biochemical reactions by means of differential equations often results in systems with a large number of variables and parameters. As this might complicate the interpretation and generalization of the obtained results, it is often desirable to reduce the complexity of the model. One way to accomplish this is by replacing the detailed reaction mechanisms of certain modules in the model by a mathematical expression that qualitatively describes the dynamical behavior of these modules. Such an approach has been widely adopted for ultrasensitive responses, for which underlying reaction mechanisms are often replaced by a single Hill equation. Also time delays are usually accounted for by using an explicit delay in delay differential equations. In contrast, however, S-shaped response curves, which are often encountered in bistable systems, are not easily modeled in such an explicit way. Here, we extend the classical Hill function into a mathematical expression that can be used to describe both ultrasensitive and S-shaped responses. We show how three ubiquitous modules (ultrasensitive responses, S-shaped responses and time delays) can be combined in different configurations and explore the dynamics of these systems. As an example, we apply our strategy to set up a model of the cell cycle consisting of multiple bistable switches, which can account for events such as DNA damage and coupling to the circadian clock in a phenomenological way.

show abstract

Recent advancement of analytical approaches for assessing Ataxia telangiectasia mutated kinase inhibitors in Ataxia telangiectasia: An overview

Rameshkumar,

ArunPrasanna,

Mahalakshmi

et al. 2024

Process Biochemistry

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FRET-Based Sorting of Live Cells Reveals Shifted Balance between PLK1 and CDK1 Activities During Checkpoint Recovery

Cited by 4 publications

References 41 publications

A modular approach for modeling the cell cycle based on functional response curves

A modular approach for modeling the cell cycle based on functional response curves

A modular approach for modeling the cell cycle based on functional response curves

Recent advancement of analytical approaches for assessing Ataxia telangiectasia mutated kinase inhibitors in Ataxia telangiectasia: An overview

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