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A Mathematical Model for DNA Damage and Repair

机译:DNA损伤和修复的数学模型

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摘要

In cells, DNA repair has to keep up with DNA damage to maintain the integrity of the genome and prevent mutagenesis and carcinogenesis. While the importance of both DNA damage and repair is clear, the impact of imbalances between both processes has not been studied. In this paper, we created a combined mathematical model for the formation of DNA adducts from oxidative estrogen metabolism followed by base excision repair (BER) of these adducts. The model encompasses a set of differential equations representing the sequence of enzymatic reactions in both damage and repair pathways. By combining both pathways, we can simulate the overall process by starting from a given time-dependent concentration of 17β-estradiol (E2) and 2′-deoxyguanosine, determine the extent of adduct formation and the correction by BER required to preserve the integrity of DNA. The model allows us to examine the effect of phenotypic and genotypic factors such as different concentrations of estrogen and variant enzyme haplotypes on the formation and repair of DNA adducts.
机译:在细胞中,DNA修复必须跟上DNA损伤的步伐,以维持基因组的完整性并防止诱变和致癌作用。尽管DNA损伤和修复的重要性很明确,但尚未研究这两个过程之间不平衡的影响。在本文中,我们创建了一个组合数学模型,用于由氧化性雌激素代谢形成DNA加合物,然后对这些加合物进行碱基切除修复(BER)。该模型包含一组微分方程,分别表示损伤和修复途径中酶促反应的顺序。通过将这两种途径结合起来,我们可以从给定的时间依赖性浓度的17β-雌二醇(E2)和2'-脱氧鸟苷开始,模拟加合物的整个过程,确定加合物的形成程度,并通过BER进行校正以保持其完整性。脱氧核糖核酸。该模型使我们能够检查表型和基因型因素,例如不同浓度的雌激素和变异酶单倍型对DNA加合物形成和修复的影响。

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