Toward a systems-level view of mitotic checkpoints.

@article{Ibrahim2015TowardAS,
  title={Toward a systems-level view of mitotic checkpoints.},
  author={Bashar Ibrahim},
  journal={Progress in biophysics and molecular biology},
  year={2015},
  volume={117 2-3},
  pages={
          217-224
        }
}
  • B. Ibrahim
  • Published 1 March 2015
  • Biology
  • Progress in biophysics and molecular biology

Figures from this paper

Mathematical analysis and modeling of DNA segregation mechanisms.

  • B. Ibrahim
  • Biology
    Mathematical biosciences and engineering : MBE
  • 2018
In this study, bistable mathematical models for both activation and silencing of mitotic checkpoints were constructed and analyzed and a one-parameter bifurcation was computed to show the realistic biochemical switches considering all signals.

Modeling potent pathways for APC/C inhibition: pivotal roles for MCC and BubR1

The presented work has successfully distinguished between five competing dynamical models of the same biological system using a systems biology approach and suggests that systems-level approach is vital for molecular biology and could also be used for compare the pathways of relevance with the objective to generate hypotheses and improve the understanding.

Spindle assembly checkpoint is sufficient for complete Cdc20 sequestering in mitotic control

  • B. Ibrahim
  • Biology
    Computational and structural biotechnology journal
  • 2015

A Dynamical Model for Activating and Silencing the Mitotic Checkpoint

The hypothesis that the SAC signal varies with increasing number of attached kinetochores, even though it might still contain toggle switches in some of its components is supported, as well as the recently-suggested rheostat switch behavior.

Unifying the mechanism of mitotic exit control in a spatiotemporal logical model

A compartmental, logical model of the MEN is presented that is capable of representing spatial aspects of regulation in parallel to control of enzymatic activity and can represent measured cell–cell variation in Spindle Position Checkpoint (SPoC) mutants.

A Mathematical Framework for Kinetochore-Driven Activation Feedback in the Mitotic Checkpoint

  • B. Ibrahim
  • Biology
    Bulletin of mathematical biology
  • 2017
Qualitative models of the human SAC should account for the positive feedback on APC/C activation driven by the kinetochores which is essential for SAC silencing, and the presented analysis allows for systems-level understanding of mitotic control.

Unifying the mechanism of mitotic exit control in a spatio-temporal logical model

A compartmental, logical model of the MEN that is capable of representing spatial aspects of regulation in parallel to control of enzymatic activity is presented and can represent measured cell-cell variation in Spindle Position Checkpoint (SPoC) mutants.

In silico spatial simulations reveal that MCC formation and excess BubR1 are required for tight inhibition of the anaphase-promoting complex.

The presented work has successfully distinguished between five potent inhibitors of the APC/C using a systems biology approach and could also be used for predicting hypotheses to design future experiments.

Septin-Associated Protein Kinases in the Yeast Saccharomyces cerevisiae

This review summarizes what the authors currently understand about how the action of septin-associated protein kinases and their substrates control information flow to drive the cell cycle into and out of mitosis, to regulate bud growth, and especially to direct timely and efficient execution of cytokinesis and cell abscission.

References

SHOWING 1-10 OF 120 REFERENCES

System-level feedbacks make the anaphase switch irreversible

The mitotic checkpoint puzzles are addressed by a proposed molecular mechanism, which involves two positive feedback loops that create a bistable response of the checkpoint to chromosomal tension.

Reverse Engineering of the Spindle Assembly Checkpoint

This work attempts to reverse-engineer the SAC network based on gene deletion phenotypes and achieves a consistent network that reproduces many of the known properties of the Sac.

Flies without a spindle checkpoint

It is shown that unlike every other reported case of SAC inactivation in metazoans, mad2-null Drosophila are viable and fertile, and their cells almost always divide correctly despite having no SAC and an accelerated 'clock', which is caused by premature degradation of cyclin B.

Anaphase spindle position is monitored by the BUB2 checkpoint

It is shown that loss of BUB2 eliminates this delay, resulting in production of anucleate cells, and spindle dynamics and cell-cycle progression in dynein and dynactin mutants of Saccharomyces cerevisiae that lack components of the spindle/kinetochore checkpoint are investigated.

SPOC alert--when chromosomes get the wrong direction.

Regulation of mitotic progression by the spindle assembly checkpoint

Recent advances in the understanding of kinetochore–checkpoint protein interactions and inhibition of the anaphase promoting complex by the MCC are highlighted.

Active Transport Can Greatly Enhance Cdc20:Mad2 Formation

It is shown that an active transport of O-Mad2 towards the spindle mid-zone increases the efficiency of Mad2-activation and this mechanism can greatly enhance the formation of Cdc20:Mad2 and gives an explanation on how the “wait-anaphase” signal can dissolve abruptly within a short time.

Sharpening the anaphase switch.

The emerging evidence that multiple, spatially and temporally regulated feedback loops ensure anaphase onset is rapid, co-ordinated and irreversible is reviewed.

Evaluating putative mechanisms of the mitotic spindle checkpoint.

The interplay between the capacities to strongly inhibit cell- cycle progression before spindle attachment and to rapidly resume cell-cycle progression once the last kinetochore is attached is described.

The spindle-assembly checkpoint in space and time

Recent molecular analyses have begun to shed light on the complex interaction of the checkpoint proteins with kinetochores — structures that mediate the binding of spindle microtubules to chromosomes in mitosis.
...