Department of Biological, Chemical and Pharmaceutical Sciences, University of Palermo, viale delle Scienze, Ed. 17, 90128 Palermo, Italy.
Université de Lorraine and CNRS, LPCT UMR 7019, F-54000 Nancy, France.
Molecules. 2022 May 19;27(10):3256. doi: 10.3390/molecules27103256.
DNA integrity is an important factor that assures genome stability and, more generally, the viability of cells and organisms. In the presence of DNA damage, the normal cell cycle is perturbed when cells activate their repair processes. Although efficient, the repair system is not always able to ensure complete restoration of gene integrity. In these cases, mutations not only may occur, but the accumulation of lesions can either lead to carcinogenesis or reach a threshold that induces apoptosis and programmed cell death. Among the different types of DNA lesions, strand breaks produced by ionizing radiation are the most toxic due to the inherent difficultly of repair, which may lead to genomic instability. In this article we show, by using classical molecular simulation techniques, that compared to canonical double-helical B-DNA, guanine-quadruplex (G4) arrangements show remarkable structural stability, even in the presence of two strand breaks. Since G4-DNA is recognized for its regulatory roles in cell senescence and gene expression, including oncogenes, this stability may be related to an evolutionary cellular response aimed at minimizing the effects of ionizing radiation.
DNA 完整性是确保基因组稳定性的一个重要因素，更广泛地说，也是确保细胞和生物体活力的一个重要因素。当细胞激活其修复过程时，在存在 DNA 损伤的情况下，正常的细胞周期会受到干扰。尽管修复系统效率很高，但它并不总是能够确保基因完整性的完全恢复。在这些情况下，不仅可能发生突变，而且损伤的积累也可能导致癌变，或者达到诱导细胞凋亡和程序性细胞死亡的阈值。在不同类型的 DNA 损伤中，由电离辐射产生的链断裂由于修复的固有难度而最为致命，这可能导致基因组不稳定。在本文中，我们使用经典的分子模拟技术表明，与规范的双螺旋 B-DNA 相比，鸟嘌呤四链体 (G4) 结构在存在两条链断裂的情况下显示出显著的结构稳定性。由于 G4-DNA 因其在细胞衰老和基因表达（包括致癌基因）中的调节作用而被识别，这种稳定性可能与细胞进化过程中的一种旨在最小化电离辐射影响的反应有关。
