Abstract
Even chromosome segregation between daughter cells during mitosis is crucial for genome integrity and is mostly regulated by proper attachments of spindle microtubules (MTs) to kinetochores. Abnormalities in this process can lead to chromosome mis-segregation and potentially result in severe developmental disorders, including aneuploidy and cancer. Merotelic attachments when tubulin MTs captured by kinetochore of one chromatid originate from both spindle poles are considered as one of the key molecular processes that cause such abnormalities. Here we present the first comprehensive three-dimensional model of metaphase, the key stage of mitosis in the context of proper chromosome segregation, and the results of its application to supercomputer simulation of kinetochore-MT attachments in metaphase. It appears that large values of the kinetochore crown angle lead to the preservation of merotelic attachments while the size of the cell and the probability of MT detachments affect only the rate of their suppression but do not interfere with the process of suppression itself. It has been demonstrated that the structure and the set of parameters of the model of mitosis have a severe impact on the results of simulations. We also compare the results of supercomputer 3D modeling of mitosis with outcomes of existing two-dimensional models.
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Acknowledgements
The project was accomplished using the equipment of the Center for Collective Use of Super High-Performance Computing Resources of the M.V. Lomonosov Moscow State University.
This work was funded by Russian Foundation for Basic Research (RFBR) grants 16-07-01064a and 19-07-01164a (to M.K and P.I.).
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Krivov, M.A., Ataullakhanov, F.I., Ivanov, P.S. (2021). Evaluation of the Effect of Cell Parameters on the Number of Microtubule Merotelic Attachments in Metaphase Using a Three-Dimensional Computer Model. In: Panuccio, G., Rocha, M., Fdez-Riverola, F., Mohamad, M., Casado-Vara, R. (eds) Practical Applications of Computational Biology & Bioinformatics, 14th International Conference (PACBB 2020). PACBB 2020. Advances in Intelligent Systems and Computing, vol 1240. Springer, Cham. https://doi.org/10.1007/978-3-030-54568-0_15
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