Laboratory of Eukaryotic Genetics, Department of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre "Kurchatov Institute", 188300 Gatchina, Russia.
Laboratory of Molecular Genetic and Recombination Technologies, Kurchatov Genome Center-Petersburg Nuclear Physics Institute, mkr. Orlova Roscha 1, Leningrad District, 188300 Gatchina, Russia.
Genes (Basel). 2021 Jul 17;12(7):1083. doi: 10.3390/genes12071083.
In the nuclear compartment of yeast, NuB4 core complex consists of three proteins, Hat1, Hat2, and Hif1, and interacts with a number of other factors. In particular, it was shown that NuB4 complex physically interacts with Hsm3p. Early we demonstrated that the gene participates in the control of replicative and reparative spontaneous mutagenesis, and that mutants increase the frequency of mutations induced by different mutagens. It was previously believed that the gene controlled only some minor repair processes in the cell, but later it was suggested that it had a chaperone function with its participation in proteasome assembly. In this work, we analyzed the properties of three , , and mutants. The results obtained showed that the Hsm3 protein may be a functional subunit of NuB4 complex. It has been shown that - and -dependent UV-induced mutagenesis is completely suppressed by inactivation of the Polη polymerase. We showed a significant role of Polη for -dependent mutagenesis at non-bipyrimidine sites (NBP sites). The efficiency of expression of (RiboNucleotid Reducase) genes after UV irradiation in and mutants was several times lower than in wild-type cells. Thus, we have presented evidence that significant increase in the dNTP levels suppress - and -dependent mutagenesis and Polη is responsible for - and -dependent mutagenesis.
在酵母的核区室中，NuB4 核心复合物由三个蛋白质（Hat1、Hat2 和 Hif1）组成，并与许多其他因素相互作用。特别是，已经表明 NuB4 复合物与 Hsm3p 具有物理相互作用。我们早期证明，基因参与控制复制和修复性自发突变，而突变体增加了不同诱变剂诱导的突变频率。以前认为基因仅控制细胞中的一些次要修复过程，但后来有人提出它具有伴侣功能，其参与蛋白酶体组装。在这项工作中，我们分析了三个、和突变体的特性。所得结果表明，Hsm3 蛋白可能是 NuB4 复合物的功能性亚基。已经表明，Polη 聚合酶的失活完全抑制了依赖于 - 和 - 的 UV 诱导的诱变。我们显示了 Polη 在非二嘧啶位点（NBP 位点）上对依赖于 - 的诱变的重要作用。UV 照射后，在和突变体中表达（核糖核苷酸还原酶）基因的效率比野生型细胞低几倍。因此，我们已经证明，dNTP 水平的显著增加抑制了依赖于 - 和 - 的诱变，而 Polη 负责依赖于 - 和 - 的诱变。
