Genetic Analysis of the Hsm3 Protein Function in Yeast <i>Saccharomyces cerevisiae</i> NuB4 Complex

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 <i>HSM3</i> participat...

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Main Authors: Tatiyana A. Evstyukhina, Elena A. Alekseeva, Dmitriy V. Fedorov, Vyacheslav T. Peshekhonov, Vladimir G. Korolev
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Genes
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Online Access:https://www.mdpi.com/2073-4425/12/7/1083
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author Tatiyana A. Evstyukhina
Elena A. Alekseeva
Dmitriy V. Fedorov
Vyacheslav T. Peshekhonov
Vladimir G. Korolev
author_facet Tatiyana A. Evstyukhina
Elena A. Alekseeva
Dmitriy V. Fedorov
Vyacheslav T. Peshekhonov
Vladimir G. Korolev
author_sort Tatiyana A. Evstyukhina
collection DOAJ
description 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 <i>HSM3</i> participates in the control of replicative and reparative spontaneous mutagenesis, and that <i>hsm3Δ</i> mutants increase the frequency of mutations induced by different mutagens. It was previously believed that the <i>HSM3</i> 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 <i>hsm3Δ</i>, <i>hif1Δ</i>, and <i>hat1Δ</i> mutants. The results obtained showed that the Hsm3 protein may be a functional subunit of NuB4 complex. It has been shown that <i>hsm3</i>- and <i>hif1</i>-dependent UV-induced mutagenesis is completely suppressed by inactivation of the Polη polymerase. We showed a significant role of Polη for <i>hsm3</i>-dependent mutagenesis at non-bipyrimidine sites (NBP sites). The efficiency of expression of <i>RNR</i> (RiboNucleotid Reducase) genes after UV irradiation in <i>hsm3Δ</i> and <i>hif1Δ</i> mutants was several times lower than in wild-type cells. Thus, we have presented evidence that significant increase in the dNTP levels suppress <i>hsm3</i>- and <i>hif1</i>-dependent mutagenesis and Polη is responsible for <i>hsm3</i>- and <i>hif1</i>-dependent mutagenesis.
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spelling doaj.art-652ee8d70d824c0b847aa5c92d9ef7662023-11-22T03:51:21ZengMDPI AGGenes2073-44252021-07-01127108310.3390/genes12071083Genetic Analysis of the Hsm3 Protein Function in Yeast <i>Saccharomyces cerevisiae</i> NuB4 ComplexTatiyana A. Evstyukhina0Elena A. Alekseeva1Dmitriy V. Fedorov2Vyacheslav T. Peshekhonov3Vladimir G. Korolev4Laboratory 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, RussiaLaboratory 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, RussiaLaboratory 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, RussiaLaboratory 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, RussiaLaboratory 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, RussiaIn 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 <i>HSM3</i> participates in the control of replicative and reparative spontaneous mutagenesis, and that <i>hsm3Δ</i> mutants increase the frequency of mutations induced by different mutagens. It was previously believed that the <i>HSM3</i> 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 <i>hsm3Δ</i>, <i>hif1Δ</i>, and <i>hat1Δ</i> mutants. The results obtained showed that the Hsm3 protein may be a functional subunit of NuB4 complex. It has been shown that <i>hsm3</i>- and <i>hif1</i>-dependent UV-induced mutagenesis is completely suppressed by inactivation of the Polη polymerase. We showed a significant role of Polη for <i>hsm3</i>-dependent mutagenesis at non-bipyrimidine sites (NBP sites). The efficiency of expression of <i>RNR</i> (RiboNucleotid Reducase) genes after UV irradiation in <i>hsm3Δ</i> and <i>hif1Δ</i> mutants was several times lower than in wild-type cells. Thus, we have presented evidence that significant increase in the dNTP levels suppress <i>hsm3</i>- and <i>hif1</i>-dependent mutagenesis and Polη is responsible for <i>hsm3</i>- and <i>hif1</i>-dependent mutagenesis.https://www.mdpi.com/2073-4425/12/7/1083yeast<i>Saccharomyces cerevisiae</i>NuB4 complex<i>HSM3</i> gene<i>HIF1</i> geneUV-induced mutagenesis
spellingShingle Tatiyana A. Evstyukhina
Elena A. Alekseeva
Dmitriy V. Fedorov
Vyacheslav T. Peshekhonov
Vladimir G. Korolev
Genetic Analysis of the Hsm3 Protein Function in Yeast <i>Saccharomyces cerevisiae</i> NuB4 Complex
Genes
yeast
<i>Saccharomyces cerevisiae</i>
NuB4 complex
<i>HSM3</i> gene
<i>HIF1</i> gene
UV-induced mutagenesis
title Genetic Analysis of the Hsm3 Protein Function in Yeast <i>Saccharomyces cerevisiae</i> NuB4 Complex
title_full Genetic Analysis of the Hsm3 Protein Function in Yeast <i>Saccharomyces cerevisiae</i> NuB4 Complex
title_fullStr Genetic Analysis of the Hsm3 Protein Function in Yeast <i>Saccharomyces cerevisiae</i> NuB4 Complex
title_full_unstemmed Genetic Analysis of the Hsm3 Protein Function in Yeast <i>Saccharomyces cerevisiae</i> NuB4 Complex
title_short Genetic Analysis of the Hsm3 Protein Function in Yeast <i>Saccharomyces cerevisiae</i> NuB4 Complex
title_sort genetic analysis of the hsm3 protein function in yeast i saccharomyces cerevisiae i nub4 complex
topic yeast
<i>Saccharomyces cerevisiae</i>
NuB4 complex
<i>HSM3</i> gene
<i>HIF1</i> gene
UV-induced mutagenesis
url https://www.mdpi.com/2073-4425/12/7/1083
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