Mathematical model of chromosomal dynamics during DNA double strand break repair in budding yeast

Biophysics and Physicobiology Pub Date : 2022-02-01 DOI:10.1101/2022.02.01.478611

Shinjiro Nakahata, Tetsushi Komoto, Masashi Fujii, A. Awazu

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引用次数: 1

Abstract

During the repair of double-strand breaks (DSBs) in DNA, active mobilizations for conformational changes in chromosomes have been widely observed in eukaryotes, from yeast to animal and plant cells. DSB-damaged loci in the yeast genome showed increased mobility and relocation to the nuclear periphery. However, the driving forces behind DSB-induced chromatin dynamics remain unclear. In this study, mathematical models of normal and DSB-damaged yeast chromosomes were developed to simulate their structural dynamics. The effects of histone degradation in the whole nucleus and the change in the physical properties of damaged loci due to the binding of SUMOylated repair proteins were considered in the model of DSB-induced chromosomes based on recent experimental results. The simulation results reproduced DSB-induced changes to structural and dynamical features by which the combination of whole nuclear histone degradation and the rigid structure formation of repair protein accumulations on damaged loci were suggested to be primary contributors to the process by which damaged loci are relocated to the nuclear periphery.

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出芽酵母DNA双链断裂修复过程中染色体动力学的数学模型

在DNA双链断裂(DSBs)修复过程中，染色体构象变化的主动动员已经在真核生物中广泛观察到，从酵母到动物和植物细胞。酵母基因组中dsb损伤的位点表现出增加的移动性和向核外周的迁移。然而，dsb诱导的染色质动力学背后的驱动力仍不清楚。在这项研究中，建立了正常和dsb损伤酵母染色体的数学模型来模拟它们的结构动力学。基于最近的实验结果，在dsb诱导的染色体模型中考虑了整个细胞核中组蛋白降解的影响以及summoylated修复蛋白结合导致的受损位点物理性质的变化。模拟结果再现了dsb诱导的结构和动力学特征的变化，通过这种变化，整个核组蛋白降解和受损位点上修复蛋白积累的刚性结构形成的结合被认为是受损位点迁移到核周围过程的主要因素。

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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Biophysics and Physicobiology

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