在真核细胞中维持基因组完整性中起重要作用的 dNTP 供应机制。
Mechanisms of dNTP supply that play an essential role in maintaining genome integrity in eukaryotic cells.
机构信息
Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Japan.
出版信息
Cancer Sci. 2010 Dec;101(12):2505-9. doi: 10.1111/j.1349-7006.2010.01719.x. Epub 2010 Sep 28.
Abstract
Optimization of intracellular concentrations of dNTPs is critical for the fidelity of DNA synthesis during DNA replication and repair because levels that are too high or too low can easily lead to increased rates of mutagenesis. Recent advances in the analysis of intracellular concentrations of dNTPs have suggested that eukaryotes use diverse mechanisms in supplying dNTPs for DNA synthesis during DNA replication and repair. The enzyme ribonucleotide reductase (RNR) is a key enzyme involved in the synthesis of dNTPs. We found that Tip60-dependent recruitment of RNR at sites of DNA damage is essential for supplying a sufficient amount of dNTPs for mammalian DNA repair. In this review, we focus on recent findings related to RNR regulation in eukaryotes of the dNTPs supplied for DNA synthesis. We also discuss the effect of this regulation on mutagenesis and tumorigenesis.
摘要
优化细胞内 dNTP 浓度对于 DNA 复制和修复过程中 DNA 合成的准确性至关重要，因为过高或过低的水平都容易导致突变率增加。最近对细胞内 dNTP 浓度的分析表明，真核生物在 DNA 复制和修复过程中使用多种机制为 DNA 合成提供 dNTP。核酶还原酶（RNR）是参与 dNTP 合成的关键酶。我们发现，Tip60 依赖性募集 RNR 到 DNA 损伤部位对于为哺乳动物 DNA 修复提供足够数量的 dNTP 是必不可少的。在这篇综述中，我们重点介绍了与真核生物中用于 DNA 合成的 dNTP 供应有关的 RNR 调节的最新发现。我们还讨论了这种调节对突变和肿瘤发生的影响。
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