A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene

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

Standard

A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene. / Gao, Yuandi; Guitton-Sert, Laure; Dessapt, Julien; Coulombe, Yan; Rodrigue, Amélie; Milano, Larissa; Blondeau, Andréanne; Larsen, Nicolai Balle; Duxin, Julien P.; Hussein, Samer; Fradet-Turcotte, Amélie; Masson, Jean Yves.

In: Nature Communications, Vol. 14, No. 1, 381, 2023.

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

Harvard

Gao, Y, Guitton-Sert, L, Dessapt, J, Coulombe, Y, Rodrigue, A, Milano, L, Blondeau, A, Larsen, NB, Duxin, JP, Hussein, S, Fradet-Turcotte, A & Masson, JY 2023, 'A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene', Nature Communications, vol. 14, no. 1, 381. https://doi.org/10.1038/s41467-023-35802-y

APA

Gao, Y., Guitton-Sert, L., Dessapt, J., Coulombe, Y., Rodrigue, A., Milano, L., Blondeau, A., Larsen, N. B., Duxin, J. P., Hussein, S., Fradet-Turcotte, A., & Masson, J. Y. (2023). A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene. Nature Communications, 14(1), [381]. https://doi.org/10.1038/s41467-023-35802-y

Vancouver

Gao Y, Guitton-Sert L, Dessapt J, Coulombe Y, Rodrigue A, Milano L et al. A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene. Nature Communications. 2023;14(1). 381. https://doi.org/10.1038/s41467-023-35802-y

Author

Gao, Yuandi ; Guitton-Sert, Laure ; Dessapt, Julien ; Coulombe, Yan ; Rodrigue, Amélie ; Milano, Larissa ; Blondeau, Andréanne ; Larsen, Nicolai Balle ; Duxin, Julien P. ; Hussein, Samer ; Fradet-Turcotte, Amélie ; Masson, Jean Yves. / A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene. In: Nature Communications. 2023 ; Vol. 14, No. 1.

Bibtex

@article{96efc1cf0bbb4df9bb0bfe9a211260e8,
title = "A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene",
abstract = "Fanconi Anemia (FA) is a rare, genome instability-associated disease characterized by a deficiency in repairing DNA crosslinks, which are known to perturb several cellular processes, including DNA transcription, replication, and repair. Formaldehyde, a by-product of metabolism, is thought to drive FA by generating DNA interstrand crosslinks (ICLs) and DNA-protein crosslinks (DPCs). However, the impact of formaldehyde on global cellular pathways has not been investigated thoroughly. Herein, using a pangenomic CRISPR-Cas9 screen, we identify EXO1 as a critical regulator of formaldehyde-induced DNA lesions. We show that EXO1 knockout cell lines exhibit formaldehyde sensitivity leading to the accumulation of replicative stress, DNA double-strand breaks, and quadriradial chromosomes, a typical feature of FA. After formaldehyde exposure, EXO1 is recruited to chromatin, protects DNA replication forks from degradation, and functions in parallel with the FA pathway to promote cell survival. In vitro, EXO1-mediated exonuclease activity is proficient in removing DPCs. Collectively, we show that EXO1 limits replication stress and DNA damage to counteract formaldehyde-induced genome instability.",
author = "Yuandi Gao and Laure Guitton-Sert and Julien Dessapt and Yan Coulombe and Am{\'e}lie Rodrigue and Larissa Milano and Andr{\'e}anne Blondeau and Larsen, {Nicolai Balle} and Duxin, {Julien P.} and Samer Hussein and Am{\'e}lie Fradet-Turcotte and Masson, {Jean Yves}",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
doi = "10.1038/s41467-023-35802-y",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene

AU - Gao, Yuandi

AU - Guitton-Sert, Laure

AU - Dessapt, Julien

AU - Coulombe, Yan

AU - Rodrigue, Amélie

AU - Milano, Larissa

AU - Blondeau, Andréanne

AU - Larsen, Nicolai Balle

AU - Duxin, Julien P.

AU - Hussein, Samer

AU - Fradet-Turcotte, Amélie

AU - Masson, Jean Yves

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - Fanconi Anemia (FA) is a rare, genome instability-associated disease characterized by a deficiency in repairing DNA crosslinks, which are known to perturb several cellular processes, including DNA transcription, replication, and repair. Formaldehyde, a by-product of metabolism, is thought to drive FA by generating DNA interstrand crosslinks (ICLs) and DNA-protein crosslinks (DPCs). However, the impact of formaldehyde on global cellular pathways has not been investigated thoroughly. Herein, using a pangenomic CRISPR-Cas9 screen, we identify EXO1 as a critical regulator of formaldehyde-induced DNA lesions. We show that EXO1 knockout cell lines exhibit formaldehyde sensitivity leading to the accumulation of replicative stress, DNA double-strand breaks, and quadriradial chromosomes, a typical feature of FA. After formaldehyde exposure, EXO1 is recruited to chromatin, protects DNA replication forks from degradation, and functions in parallel with the FA pathway to promote cell survival. In vitro, EXO1-mediated exonuclease activity is proficient in removing DPCs. Collectively, we show that EXO1 limits replication stress and DNA damage to counteract formaldehyde-induced genome instability.

AB - Fanconi Anemia (FA) is a rare, genome instability-associated disease characterized by a deficiency in repairing DNA crosslinks, which are known to perturb several cellular processes, including DNA transcription, replication, and repair. Formaldehyde, a by-product of metabolism, is thought to drive FA by generating DNA interstrand crosslinks (ICLs) and DNA-protein crosslinks (DPCs). However, the impact of formaldehyde on global cellular pathways has not been investigated thoroughly. Herein, using a pangenomic CRISPR-Cas9 screen, we identify EXO1 as a critical regulator of formaldehyde-induced DNA lesions. We show that EXO1 knockout cell lines exhibit formaldehyde sensitivity leading to the accumulation of replicative stress, DNA double-strand breaks, and quadriradial chromosomes, a typical feature of FA. After formaldehyde exposure, EXO1 is recruited to chromatin, protects DNA replication forks from degradation, and functions in parallel with the FA pathway to promote cell survival. In vitro, EXO1-mediated exonuclease activity is proficient in removing DPCs. Collectively, we show that EXO1 limits replication stress and DNA damage to counteract formaldehyde-induced genome instability.

U2 - 10.1038/s41467-023-35802-y

DO - 10.1038/s41467-023-35802-y

M3 - Journal article

C2 - 36693839

AN - SCOPUS:85146738644

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 381

ER -

ID: 335965145