A mathematical model of kinetochore-microtubule attachment regulated by Aurora A activity gradient describes chromosome oscillation and correction of erroneous attachments.

IF 1.3 4区医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedical Research-tokyo Pub Date : 2021-01-01 DOI:10.2220/biomedres.42.203

Manuel Alejandro Campos Medina, Kenji Iemura, Akatsuki Kimura, Kozo Tanaka

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引用次数: 1

Abstract

Chromosome oscillation during metaphase is attenuated in cancer cell lines, concomitant with the reduction of Aurora A activity on kinetochores, which results in reduced mitotic fidelity. To verify the correlation between Aurora A activity, chromosome oscillation, and error correction efficiency, we developed a mathematical model of kinetochore-microtubule dynamics, based on stochastic attachment/detachment events regulated by Aurora A activity gradient centered at spindle poles. The model accurately reproduced the oscillatory movements of chromosomes, which were suppressed not only when Aurora A activity was inhibited, but also when it was upregulated, mimicking the situation in cancer cells. Our simulation also predicted efficient correction of erroneous attachments through chromosome oscillation, which was hampered by both inhibition and upregulation of Aurora A activity. Our model provides a framework to understand the physiological role of chromosome oscillation in the correction of erroneous attachments that is intrinsically related to Aurora A activity.

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一个由极光A活性梯度调控的着丝点-微管附着的数学模型描述了染色体振荡和错误附着的校正。

在癌细胞系中，染色体振荡在中期减弱，同时着丝点上Aurora A活性降低，导致有丝分裂保真度降低。为了验证极光A活性、染色体振荡和纠错效率之间的相关性，我们建立了一个基于以纺锤极为中心的极光A活性梯度调节的随机附着/脱离事件的着丝点-微管动力学数学模型。该模型准确地再现了染色体的振荡运动，不仅在极光A活性被抑制时，而且在极光A活性上调时，染色体的振荡运动也受到抑制，模拟了癌细胞的情况。我们的模拟还预测了通过染色体振荡有效地纠正错误的附着，这受到极光A活性的抑制和上调的阻碍。我们的模型提供了一个框架来理解染色体振荡在纠正与极光a活性内在相关的错误附着中的生理作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedical Research-tokyo 医学-医学：研究与实验

CiteScore

2.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..