细胞dNTP库的稳态维持与基因组稳定性
收稿日期: 2021-10-16
修回日期: 2021-12-14
网络出版日期: 2021-12-28
基金资助
国家自然科学基金项目编号(81971905);福建省自然科学基金项目资助编号(FJHJF-L-2019-4);福建省自然科学基金项目资助编号(JT180009)
Maintenance of dNTP pool homeostasis and genomic stability
Received date: 2021-10-16
Revised date: 2021-12-14
Online published: 2021-12-28
Supported by
Supported by the National Natural Science Foundation of China No(81971905);the Natural Science Foundation of Fujian Province Nos(FJHJF-L-2019-4);the Natural Science Foundation of Fujian Province Nos(JT180009)
作为DNA合成的重要前体,细胞中4种脱氧核糖核苷三磷酸(dATP、dTTP、dGTP和dCTP)是DNA复制、重组和修复所必需的原材料,而DNA的正确合成及其完整性则是基因组稳定性的重要体现,因此dNTP库状态的稳定对维持基因组的稳定进而保证细胞的稳定至关重要。从dNTP库的质量上讲,一些异质dNTP如氧化的dNTP掺入DNA容易引发碱基替换甚至DNA断裂重排,会极大地损害基因组的稳定性。但与此同时,细胞也进化出了相应的NTP焦磷酸酶将其清除,并且细胞也会通过形成DNA损伤修复网络来校正损伤的DNA及修复DNA缺口。从dNTP库的数量上讲,dNTP的浓度及比例失衡也会造成碱基突变和移码突变,这同样会引发基因组不的稳定性,由此细胞进化出了庞大的酶控网络以对其进行精密调控。本文主要综述细胞内dNTP库组分受损的潜在危害及受损dNTP的清除和dNTP库组分间平衡的调控及失衡的后果,最后介绍了与dNTP库稳态相关的临床疾病,旨在为细胞dNTP库的稳态维持与基因组稳定性的相关性研究提供一定的思路方向,最终为相关疾病的治疗提供部分理论依据。
刘聪, 冯佳妮, 李玮玮, 朱伟伟, 薛云新, 王岱, 赵西林 . 细胞dNTP库的稳态维持与基因组稳定性[J]. 遗传, 2022 , 44(2) : 96 -106 . DOI: 10.16288/j.yczz.21-211
As an important precursor for DNA synthesis, the four deoxyribonucleoside triphosphates (dATP, dTTP, dGTP, and dCTP) are necessary raw materials for DNA replication, recombination, and repair in cells. The correct synthesis and integrity of DNA are important manifestations of the genome stability, so the stability of the dNTP library state is essential to maintain the stability of the genome and the cell. In terms of the quality of the dNTP library, the incorporation of some heterogeneous dNTPs, such as oxidized dNTPs, into DNA can easily cause base substitutions and even DNA breaks and rearrangements, which will greatly damage the stability of the genome. At the same time, the cell has also evolved the corresponding NTP pyrophosphatase to remove it, and to correct the damaged DNA and repair the DNA gap by forming a DNA damage repair network. In terms of the number of dNTP libraries, the imbalance of the dNTP concentration and ratio will also cause base and frameshift mutations, which will also cause genome instability. As a result, cells have evolved a huge enzyme-controlled network to carry them out under precise control. This article mainly reviews the potential harm of damage to dNTP library components in cells, the clearance of damaged dNTPs, the regulation on the balance between dNTP library components, and finally discusses clinical diseases related to dNTP library homeostasis. It provides insights on the research of the correlation between the stability of the cellular dNTP library and the genome, and finally provides some theoretical basis for the treatment of related diseases.
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