Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase—Pol ε Interaction
Abstract
:1. Introduction
2. Results
2.1. Psf1-100 Impairs the Interaction between GINS and Pol ε, Which Results in Impeded DNA Synthesis
2.2. Increased Formation of Single-Stranded DNA in psf1-100 Cells
2.3. Homologous Recombination Rescues psf1-100 Cells
2.4. Pol ζ Exerts Its Mutagenic Activity in psf1-100 Cells Mainly in G2 Phase
2.5. HR and Pol ζ-Dependent Synthesis Play Important Roles in psf1-100 Cells
2.6. The psf1-100 Allele Facilitates Primer-Template Rearrangements, Frameshift Formation and the Instability of Repeated DNA Tracts
3. Discussion
4. Materials and Methods
4.1. Strains, Media and General Methods
4.2. Construction of Yeast Strains
4.3. Protein Purification
4.4. Pol ε-GINS In Vitro Interaction Assay
4.5. In Vitro Replication Assay
4.6. Measurement of Spontaneous Mutation Frequency at the CAN1 Locus
4.7. Calculation of Mutation Rates and Statistical Analysis
4.8. CANR Mutation Spectrum
4.9. Detection of Recombination Events
4.10. Determination of UV Radiation Sensitivity and UV-Induced Mutagenesis at the CAN1 Locus
4.11. Synchronization in G1 Phase with α-Factor
4.12. Flow Cytometry Analysis
4.13. Western Blot Analysis
4.14. Identification of Rad52, Rad51 and Rfa1 Foci by Fluorescence Microscopy
4.15. Yeast Viability Assessment
4.16. Stability of Repetitive Sequences
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
BIR | Break-induced recombination |
CMG | Cdc45, Mcm2–7, GINS complex |
CMGE | Cdc45, Mcm2–7, GINS, DNA polymerase epsilon (Pol ε) complex |
GINS | Psf1, Psf2, Psf3, Sld5 complex |
HR | Homologous recombination |
TS | Template switch |
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Genotype | CAN1 Mutation Rate | p-Value 2 | ||
---|---|---|---|---|
× 10−8 | 95% Confidence Intervals | Relative 1 | ||
WT | 176.0 | 148.4–247.0 | 1.0 | |
G2-REV3 | 232.5 | 216.7–246.1 | 1.5 | 0.059951 |
rev3Δ | 95.3 | 88.4–117.6 | 0.6 | 0.000855 |
psf1-100 | 331.9 | 299.8–415.1 | 2.0 | |
psf1-100 G2-REV3 | 308.6 | 301.4–382.3 | 2.0 | 0.783131 |
psf1-100 rev3Δ | 76.5 | 69.5–87.8 | 0.5 | 0.000017 |
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Denkiewicz-Kruk, M.; Jedrychowska, M.; Endo, S.; Araki, H.; Jonczyk, P.; Dmowski, M.; Fijalkowska, I.J. Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase—Pol ε Interaction. Int. J. Mol. Sci. 2020, 21, 9484. https://doi.org/10.3390/ijms21249484
Denkiewicz-Kruk M, Jedrychowska M, Endo S, Araki H, Jonczyk P, Dmowski M, Fijalkowska IJ. Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase—Pol ε Interaction. International Journal of Molecular Sciences. 2020; 21(24):9484. https://doi.org/10.3390/ijms21249484
Chicago/Turabian StyleDenkiewicz-Kruk, Milena, Malgorzata Jedrychowska, Shizuko Endo, Hiroyuki Araki, Piotr Jonczyk, Michal Dmowski, and Iwona J. Fijalkowska. 2020. "Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase—Pol ε Interaction" International Journal of Molecular Sciences 21, no. 24: 9484. https://doi.org/10.3390/ijms21249484