Deoxyribonucleoside triphosphate levels: A critical factor in the maintenance of genetic stability

Bernard A. Kunz , Susanne E. Kohalmi , Thomas A. Kunkel , Christopher K. Mathews , Evan M. McIntosh , John A. Reidy
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Abstract

DNA precursor pool imbalances can elicit a variety of genetic effects and modulate the genotoxicity of certain DNA-damaging agents. These and other observations indicate that the control of DNA precursor concentrations is essential for the maintenance of genetic stability, and suggest that factors which offset this control may contribute to environmental mutagenesis and carcinogenesis. In this article, we review the biochemical and genetic mechanisms responsible for regulating the production and relative amounts of intracellular DNA precursors, describe the many outcomes of perturbations in DNA precursor levels, and discuss implications of such imbalances for sensitivity to DNA-damaging agents, population monitoring, and human diseases.

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脱氧核糖核苷三磷酸水平:维持遗传稳定性的关键因素
DNA前体库失衡可以引发各种遗传效应,并调节某些DNA损伤剂的遗传毒性。这些和其他观察结果表明,控制DNA前体浓度对维持遗传稳定性至关重要,并表明抵消这种控制的因素可能有助于环境诱变和致癌。在这篇文章中,我们回顾了负责调节细胞内DNA前体的产生和相对量的生化和遗传机制,描述了DNA前体水平扰动的许多结果,并讨论了这种失衡对DNA损伤因子敏感性、群体监测和人类疾病的影响。
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