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

Ibrahim, Bashar

doi:10.1016/j.csbj.2015.03.006

Cited by 12 publications

(2 citation statements)

References 66 publications

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“…When DNA damage, mutations or other abnormal conditions occur, the cell cycle checkpoint can timely block or delay cell cycle progression to repair the damaged DNA or regulate cell apoptosis 51 , 52 . Cell cycle checkpoints can be divided into three types according to their different functions, such as DNA replication checkpoints, DNA damage checkpoints and spindle assembly checkpoints 53 - 55 . When cells are challenged with genotoxic stress, the ATM/ATR family of kinases can phosphorylate the histone H2AX.…”

Section: Discussionmentioning

confidence: 99%

Mycotoxin zearalenone exposure impairs genomic stability of swine follicular granulosa cells in vitro

Liu¹,

Wu²,

Sun³

et al. 2018

Int. J. Biol. Sci.

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Zearalenone (ZEA), a metabolite of Fusarium fungi, is commonly found on moldy grains. Because it can competitively combine to estrogen receptor to disrupt estrogenic signaling, it has been reported to have serious adverse effects on animal reproduction systems. In order to explore the genotoxic effects of ZEA exposure on ovarian somatic cells, porcine granulosa cells were exposed to 10 μM and 30 μM ZEA for 24 or 72 h in vitro. The results showed that ZEA exposure for 24 h remarkably reduced the proliferation of porcine granulosa cells in a dose-dependent manner as determined by MTT analysis and flow cytometry. Furthermore, exposure to ZEA for 72 h induced apoptosis, and RNA sequence analysis also revealed that the expression of apoptosis related genes were altered. RT-qPCR, immunofluorescence and western blot analysis further confirmed the expression of DNA damage and repair related genes (γ-H2AX, BRCA1, RAD51 and PRKDC) were increased in ZEA exposed granulosa cells. When the estrogen antagonist, tamoxifen, was added with ZEA in the culture medium, the DNA damage and repairment by ZEA returned to normal level. Collectively, these results illustrate that ZEA disrupts genome stability and inhibits growth of porcine granulosa cells via the estrogen receptors which may promote granulosa cell apoptosis when the DNA repair system is not enough to rescue this serious damage.

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Section: Discussionmentioning

confidence: 99%

Mycotoxin zearalenone exposure impairs genomic stability of swine follicular granulosa cells in vitro

Liu¹,

Wu²,

Sun³

et al. 2018

Int. J. Biol. Sci.

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show abstract

“…Also, the different components often interact nonlinearly in space and time, and in the presence of various feedback loops, which lead to remarkable phenomena that are difficult to predict [15,28,36,16,14,61]. Mathematical models have helped to illuminate fundamental modules of the SAC controls [8,53,21,40,20,22,27,45,37,25,13,24,26,29,3]. These models yet conceived SAC activation on details molecular level in order to distinguish between different pathways.…”

Section: Introductionmentioning

confidence: 99%

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

Ibrahim

2017

Bull Math Biol

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Proliferating cells properly divide into their daughter cells through a process that is mediated by kinetochores, protein-complexes that assemble at the centromere of each sister chromatid. Each kinetochore has to establish a tight bipolar attachment to the spindle apparatus before sister chromatid separation is initiated. The spindle assembly checkpoint (SAC) links the biophysical attachment status of the kinetochores to mitotic progression and ensures that even a single misaligned kinetochore keeps the checkpoint active. The mechanism by which this is achieved is still elusive. Current computational models of the human SAC disregard important biochemical properties by omitting any kind of feedback loop, proper kinetochore signals, and other spatial properties such as the stability of the system and diffusion effects. To allow for more realistic in silico study of the dynamics of the SAC model, a minimal mathematical framework for SAC activation and silencing is introduced. A nonlinear ordinary differential equation model successfully reproduces bifurcation signaling switches with attachment of all 92 kinetochores and activation of APC/C by kinetochore-driven feedback. A partial differential equation model and mathematical linear stability analyses indicate the influence of diffusion and system stability. The conclusion is that quantitative 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. Experimental diffusion coefficients for MCC subcomplexes are found to be insufficient for rapid APC/C inhibition. The presented analysis allows for systems-level understanding of mitotic control, and the minimal new model can function as a basis for developing further quantitative-integrative models of the cell division cycle.

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Trends in mathematical modeling of host–pathogen interactions

Ewald

Sieber

Garde

et al. 2019

Cell. Mol. Life Sci.

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Pathogenic microorganisms entail enormous problems for humans, livestock, and crop plants. A better understanding of the different infection strategies of the pathogens enables us to derive optimal treatments to mitigate infectious diseases or develop vaccinations preventing the occurrence of infections altogether. In this review, we highlight the current trends in mathematical modeling approaches and related methods used for understanding host-pathogen interactions. Since these interactions can be described on vastly different temporal and spatial scales as well as abstraction levels, a variety of computational and mathematical approaches are presented. Particular emphasis is placed on dynamic optimization, game theory, and spatial modeling, as they are attracting more and more interest in systems biology. Furthermore, these approaches are often combined to illuminate the complexities of the interactions between pathogens and their host. We also discuss the phenomena of molecular mimicry and crypsis as well as the interplay between defense and counter defense. As a conclusion, we provide an overview of method characteristics to assist non-experts in their decision for modeling approaches and interdisciplinary understanding.

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

Cited by 12 publications

References 66 publications

Mycotoxin zearalenone exposure impairs genomic stability of swine follicular granulosa cells in vitro

Mycotoxin zearalenone exposure impairs genomic stability of swine follicular granulosa cells in vitro

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

Trends in mathematical modeling of host–pathogen interactions

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