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Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase—Pol ε Interaction

Denkiewicz-Kruk, Milena and Jedrychowska, Malgorzata and Endo, Shizuko and Araki, Hiroyuki and Jonczyk, Piotr and Dmowski, Michal and Fijalkowska, Iwona J. (2020) Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase—Pol ε Interaction. International Journal of Molecular Sciences, 21 (24). p. 9484. ISSN 1422-0067

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Official URL: https://www.mdpi.com/1422-0067/21/24/9484


The CMG complex (Cdc45, Mcm2–7, GINS (Psf1, 2, 3, and Sld5)) is crucial for both DNA replication initiation and fork progression. The CMG helicase interaction with the leading strand DNA polymerase epsilon (Pol ε) is essential for the preferential loading of Pol ε onto the leading strand, the stimulation of the polymerase, and the modulation of helicase activity. Here, we analyze the consequences of impaired interaction between Pol ε and GINS in Saccharomyces cerevisiae cells with the psf1-100 mutation. This significantly affects DNA replication activity measured in vitro, while in vivo, the psf1-100 mutation reduces replication fidelity by increasing slippage of Pol ε, which manifests as an elevated number of frameshifts. It also increases the occurrence of single-strandedDNA(ssDNA) gaps and the demand for homologous recombination. The psf1-100 mutant shows elevated recombination rates and synthetic lethality with rad52D. Additionally, we observe increased participation of DNA polymerase zeta (Pol ζ) in DNA synthesis. We conclude that the impaired interaction between GINS and Pol ε requires enhanced involvement of error-prone Pol ζ, and increased participation of recombination as a rescue mechanism for recovery of impaired replication forks.

Item Type:Article
Uncontrolled Keywords:CMGE helicase-polymerase complex; GINS complex; PSF1/GINS1; DNA polymerase epsilon; Pol ε"; polymerase zeta; Pol ζ; recombination; DRIM; DNA replication fidelity; genetic instability; repeat tracts instability
Subjects:Q Science > Q Science (General)
Q Science > QR Microbiology
Divisions:Laboratory of Mutagenesis and DNA Repair
ID Code:1958
Deposited By: dr Michał Dmowski
Deposited On:05 Jan 2021 10:39
Last Modified:05 Jan 2021 10:39

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