Ethanol exposure increases mutation rate through error-prone polymerases

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Ethanol exposure increases mutation rate through error-prone polymerases. / Voordeckers, Karin; Colding, Camilla; Grasso, Lavinia; Pardo, Benjamin; Hoes, Lore; Kominek, Jacek; Gielens, Kim; Dekoster, Kaat; Gordon, Jonathan; Van der Zande, Elisa; Bircham, Peter; Swings, Toon; Michiels, Jan; Van Loo, Peter; Nuyts, Sandra; Pasero, Philippe; Lisby, Michael; Verstrepen, Kevin J.

In: Nature Communications, Vol. 11, 3664, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Voordeckers, K, Colding, C, Grasso, L, Pardo, B, Hoes, L, Kominek, J, Gielens, K, Dekoster, K, Gordon, J, Van der Zande, E, Bircham, P, Swings, T, Michiels, J, Van Loo, P, Nuyts, S, Pasero, P, Lisby, M & Verstrepen, KJ 2020, 'Ethanol exposure increases mutation rate through error-prone polymerases', Nature Communications, vol. 11, 3664. https://doi.org/10.1038/s41467-020-17447-3

APA

Voordeckers, K., Colding, C., Grasso, L., Pardo, B., Hoes, L., Kominek, J., Gielens, K., Dekoster, K., Gordon, J., Van der Zande, E., Bircham, P., Swings, T., Michiels, J., Van Loo, P., Nuyts, S., Pasero, P., Lisby, M., & Verstrepen, K. J. (2020). Ethanol exposure increases mutation rate through error-prone polymerases. Nature Communications, 11, [3664]. https://doi.org/10.1038/s41467-020-17447-3

Vancouver

Voordeckers K, Colding C, Grasso L, Pardo B, Hoes L, Kominek J et al. Ethanol exposure increases mutation rate through error-prone polymerases. Nature Communications. 2020;11. 3664. https://doi.org/10.1038/s41467-020-17447-3

Author

Voordeckers, Karin ; Colding, Camilla ; Grasso, Lavinia ; Pardo, Benjamin ; Hoes, Lore ; Kominek, Jacek ; Gielens, Kim ; Dekoster, Kaat ; Gordon, Jonathan ; Van der Zande, Elisa ; Bircham, Peter ; Swings, Toon ; Michiels, Jan ; Van Loo, Peter ; Nuyts, Sandra ; Pasero, Philippe ; Lisby, Michael ; Verstrepen, Kevin J. / Ethanol exposure increases mutation rate through error-prone polymerases. In: Nature Communications. 2020 ; Vol. 11.

Bibtex

@article{49e30c352ca14a2fb7d598d54375899f,
title = "Ethanol exposure increases mutation rate through error-prone polymerases",
abstract = "Ethanol is a ubiquitous environmental stressor that is toxic to all lifeforms. Here, we use the model eukaryote Saccharomyces cerevisiae to show that exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate. Specifically, we find that ethanol slows down replication and affects localization of Mrc1, a conserved protein that helps stabilize the replisome. In addition, ethanol exposure also results in the recruitment of error-prone DNA polymerases to the replication fork. Interestingly, preventing this recruitment through mutagenesis of the PCNA/Pol30 polymerase clamp or deleting specific error-prone polymerases abolishes the mutagenic effect of ethanol. Taken together, this suggests that the mutagenic effect depends on a complex mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases. Apart from providing a general mechanistic framework for the mutagenic effect of ethanol, our findings may also provide a route to better understand and prevent ethanol-associated carcinogenesis in higher eukaryotes.",
keywords = "STRESS-INDUCED MUTAGENESIS, DNA-REPLICATION STRESS, SACCHAROMYCES-CEREVISIAE, MISFOLDED PROTEINS, CELL-CYCLE, ALCOHOL, YEAST, REPAIR, ACETALDEHYDE, GENOME",
author = "Karin Voordeckers and Camilla Colding and Lavinia Grasso and Benjamin Pardo and Lore Hoes and Jacek Kominek and Kim Gielens and Kaat Dekoster and Jonathan Gordon and {Van der Zande}, Elisa and Peter Bircham and Toon Swings and Jan Michiels and {Van Loo}, Peter and Sandra Nuyts and Philippe Pasero and Michael Lisby and Verstrepen, {Kevin J.}",
year = "2020",
doi = "10.1038/s41467-020-17447-3",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Ethanol exposure increases mutation rate through error-prone polymerases

AU - Voordeckers, Karin

AU - Colding, Camilla

AU - Grasso, Lavinia

AU - Pardo, Benjamin

AU - Hoes, Lore

AU - Kominek, Jacek

AU - Gielens, Kim

AU - Dekoster, Kaat

AU - Gordon, Jonathan

AU - Van der Zande, Elisa

AU - Bircham, Peter

AU - Swings, Toon

AU - Michiels, Jan

AU - Van Loo, Peter

AU - Nuyts, Sandra

AU - Pasero, Philippe

AU - Lisby, Michael

AU - Verstrepen, Kevin J.

PY - 2020

Y1 - 2020

N2 - Ethanol is a ubiquitous environmental stressor that is toxic to all lifeforms. Here, we use the model eukaryote Saccharomyces cerevisiae to show that exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate. Specifically, we find that ethanol slows down replication and affects localization of Mrc1, a conserved protein that helps stabilize the replisome. In addition, ethanol exposure also results in the recruitment of error-prone DNA polymerases to the replication fork. Interestingly, preventing this recruitment through mutagenesis of the PCNA/Pol30 polymerase clamp or deleting specific error-prone polymerases abolishes the mutagenic effect of ethanol. Taken together, this suggests that the mutagenic effect depends on a complex mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases. Apart from providing a general mechanistic framework for the mutagenic effect of ethanol, our findings may also provide a route to better understand and prevent ethanol-associated carcinogenesis in higher eukaryotes.

AB - Ethanol is a ubiquitous environmental stressor that is toxic to all lifeforms. Here, we use the model eukaryote Saccharomyces cerevisiae to show that exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate. Specifically, we find that ethanol slows down replication and affects localization of Mrc1, a conserved protein that helps stabilize the replisome. In addition, ethanol exposure also results in the recruitment of error-prone DNA polymerases to the replication fork. Interestingly, preventing this recruitment through mutagenesis of the PCNA/Pol30 polymerase clamp or deleting specific error-prone polymerases abolishes the mutagenic effect of ethanol. Taken together, this suggests that the mutagenic effect depends on a complex mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases. Apart from providing a general mechanistic framework for the mutagenic effect of ethanol, our findings may also provide a route to better understand and prevent ethanol-associated carcinogenesis in higher eukaryotes.

KW - STRESS-INDUCED MUTAGENESIS

KW - DNA-REPLICATION STRESS

KW - SACCHAROMYCES-CEREVISIAE

KW - MISFOLDED PROTEINS

KW - CELL-CYCLE

KW - ALCOHOL

KW - YEAST

KW - REPAIR

KW - ACETALDEHYDE

KW - GENOME

U2 - 10.1038/s41467-020-17447-3

DO - 10.1038/s41467-020-17447-3

M3 - Journal article

C2 - 32694532

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3664

ER -

ID: 247155573