Evidence map›Paper›PMID 36693839›Full record

ArticleNature communications2023

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

Yuandi Gao, Laure Guitton-Sert, Julien Dessapt, Yan Coulombe, Amélie Rodrigue, Larissa Milano, Andréanne Blondeau, Nicolai Balle Larsen, Julien P Duxin, Samer Hussein and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 25 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Yuandi Gao *CHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.ORCID 0000-0002-1828-9776
Laure Guitton-Sert *CHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.ORCID 0000-0002-4529-5493
Julien DessaptCHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.
Yan CoulombeCHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.
Amélie RodrigueCHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.
Larissa MilanoCHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.ORCID 0000-0003-0834-4249
Andréanne BlondeauCHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.
Nicolai Balle LarsenNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.ORCID 0000-0001-5105-7056
Julien P DuxinNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Samer HusseinCHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.
Amélie Fradet-TurcotteCHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada.ORCID 0000-0002-5431-8650
Jean-Yves MassonCHU de Québec Research Center, Oncology Division, Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, 9 McMahon, Québec City, QC, G1R 3S3, Canada. Jean-Yves.Masson@crchudequebec.ulaval.ca.ORCID 0000-0002-4403-7169
Université Laval · CAUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

CRISPR-Cas SystemsDrug ToleranceExodeoxyribonucleasesFanconi AnemiaFormaldehydeDNADNA DamageDNA RepairDNA Repair EnzymesDNA ReplicationGenomic InstabilityHumansDNADNA Repair EnzymesEXO1 protein, humanExodeoxyribonucleasesFormaldehyde

Identifiers

PMID36693839
PMCPMC9873647
OpenAlexW4317829694

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.