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

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

研究成果: Article査読

1 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)203-219
ページ数17
ジャーナルBiomedical Research (Japan)
42
5
DOI
出版ステータスPublished - 2021

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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