Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO
Abstract
:1. Introduction
2. Materials and Methods
2.1. Yeast Strains
2.2. Media, Culture, and Assay Conditions
2.3. LC-MS/MS Data Acquisition
2.4. LC-MS/MS Data Processing
2.5. Real-Time qPCR Analysis
2.6. Cloning of RNR Genes
2.7. Western Blot Analysis of RNR Subunits
2.8. Cycloheximide Chase
2.9. Creation of Yeast Mutants and Inhibitor Plate Assay
3. Results
3.1. Proteomic Analysis Indicates Increased Levels of RNR Subunits in the YPL Strain Compared to the WT Strain
3.2. Deregulation of the Proteasome Leads to Enhanced Levels of Large RNR Subunits
3.3. Rnr1 Is a Proteasome Substrate
3.4. HU Reverses the 4-NQO Hyper Resistance Phenotype in the YPL Strain
3.5. Lack of RNR Regulatory Proteins Sensitizes WT and YPL Strains to HU and 4-NQO
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Name of the Strain | Genotype | Source |
---|---|---|
BY4742 | MAT α; his3Δ1; leu2Δ0; lys2Δ0; ura3Δ0 | Euroscarf, Oberursel, Germany |
YPL | BY4742 derivative MAT α; his3Δ1; leu2Δ0; lys2Δ0; ura3Δ0, pre1–8 | [11] |
WT△sml1 | BY4741 YML058W::LEU2 | This work |
WT△ydj1 | BY4741 YNL064C::LEU2 | –//– |
YPL△sml1 | BY4742 YML058W::LEU2 | –//– |
YPL△ydj1 | YPL YNL064C::LEU2 | –//– |
Protein Name | Log2FC | −Log10FDR 1 |
---|---|---|
RNR1 | 1.52 | 2.16 |
RNR3 | 1.57 | 3.38 |
MCM3 | 1.36 | 1.74 |
MCM6 | 1.23 | 2.55 |
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Spasskaya, D.S.; Kulagin, K.A.; Grineva, E.N.; Osipova, P.J.; Poddubko, S.V.; Bubis, J.A.; Kazakova, E.M.; Kusainova, T.T.; Gorshkov, V.A.; Kjeldsen, F.; et al. Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO. J. Fungi 2023, 9, 351. https://doi.org/10.3390/jof9030351
Spasskaya DS, Kulagin KA, Grineva EN, Osipova PJ, Poddubko SV, Bubis JA, Kazakova EM, Kusainova TT, Gorshkov VA, Kjeldsen F, et al. Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO. Journal of Fungi. 2023; 9(3):351. https://doi.org/10.3390/jof9030351
Chicago/Turabian StyleSpasskaya, Daria S., Kirill A. Kulagin, Evgenia N. Grineva, Pamila J. Osipova, Svetlana V. Poddubko, Julia A. Bubis, Elizaveta M. Kazakova, Tomiris T. Kusainova, Vladimir A. Gorshkov, Frank Kjeldsen, and et al. 2023. "Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO" Journal of Fungi 9, no. 3: 351. https://doi.org/10.3390/jof9030351