Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint.
Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint.
复制标题
DOI：
10.1093/nar/gkq128
复制
发表时间：
2010-07
影响因子：
14.9
通讯作者：
Chabes A
中科院分区：
文献类型：
--
作者：
Kumar D;Viberg J;Nilsson AK;Chabes A
脱氧核糖核苷三磷酸（dNTPs）的平衡供应是基因组忠实复制的关键先决条件之一。总体浓度和个体dNTP（dATP、dTTP、dGTP和dCTP）之间的平衡均主要由核糖核苷酸还原酶（RNR）严格调节。我们询问dNTP池失衡是否会干扰细胞周期进程，并通过S期检查点检测到，S期检查点是一种响应DNA损伤或复制阻滞而激活的基因组监视机制。通过在酿酒酵母RNR的变构特异性位点的环2中引入单个氨基酸取代，我们获得了具有各种dNTP池不平衡的菌株的集合。即使是轻度dNTP池失衡也具有致突变性，但不同dNTP池失衡的致突变潜力与其严重程度无直接相关性。S期检查点通过一个或几个dNTP的耗尽而激活。相反，当没有dNTP限制DNA复制时，即使极端和致突变的dNTP池失衡也不会激活S期检查点，也不会干扰细胞周期进程。
A balanced supply of deoxyribonucleoside triphosphates (dNTPs) is one of the key prerequisites for faithful genome duplication. Both the overall concentration and the balance among the individual dNTPs (dATP, dTTP, dGTP, and dCTP) are tightly regulated, primarily by the enzyme ribonucleotide reductase (RNR). We asked whether dNTP pool imbalances interfere with cell cycle progression and are detected by the S-phase checkpoint, a genome surveillance mechanism activated in response to DNA damage or replication blocks. By introducing single amino acid substitutions in loop 2 of the allosteric specificity site of Saccharomyces cerevisiae RNR, we obtained a collection of strains with various dNTP pool imbalances. Even mild dNTP pool imbalances were mutagenic, but the mutagenic potential of different dNTP pool imbalances did not directly correlate with their severity. The S-phase checkpoint was activated by the depletion of one or several dNTPs. In contrast, when none of the dNTPs was limiting for DNA replication, even extreme and mutagenic dNTP pool imbalances did not activate the S-phase checkpoint and did not interfere with the cell cycle progression.
登录
查看更多内容
影响因子：
30.8
作者：
Bourdon, Alice;Minai, Limor;Rotig, Agnes
通讯作者：
Rotig, Agnes
影响因子：
9.8
作者：
Tyynismaa, Henna;Ylikallio, Emil;Suomalainen, Anu
通讯作者：
Suomalainen, Anu
影响因子：
10.5
作者：
ELLEDGE, SJ;DAVIS, RW
通讯作者：
DAVIS, RW
影响因子：
14.9
作者：
Sabouri N;Viberg J;Goyal DK;Johansson E;Chabes A
通讯作者：
Chabes A
影响因子：
3.8
作者：
Navadgi-Patil VM;Burgers PM
通讯作者：
Burgers PM