Evidence map›Paper›PMID 37478847›Full record

ArticleMolecular cell2023

Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens.

Yichao Zhao, Daniel Tabet, Diana Rubio Contreras, Linjiang Lao, Arne Nedergaard Kousholt, Jochen Weile, Henrique Melo, Lisa Hoeg, Sumin Feng, Atina G Coté and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

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  9. YTHDC1 mThe EMBO journal · 2024
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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

17 authors at 3 institutions in 3 countries.

Yichao ZhaoLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Daniel TabetLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Diana Rubio ContrerasInstituto de Biomedicina de Sevilla (IBiS), Manuel Siurot s/n, 41013 Sevilla, Spain.
Linjiang LaoLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Arne Nedergaard KousholtDivision of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, 1066CX Amsterdam, the Netherlands.
Jochen WeileLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Donnelly Centre and Department of Computer Science, University of Toronto, 160 College Street, Toronto M5S 3E1, Canada.
Henrique MeloLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Lisa HoegLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Sumin FengLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Atina G CotéLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Zhen-Yuan LinLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Dheva SetiaputraLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Jos JonkersDivision of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, 1066CX Amsterdam, the Netherlands.
Anne-Claude GingrasLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Fernando Gómez HerrerosInstituto de Biomedicina de Sevilla (IBiS), Manuel Siurot s/n, 41013 Sevilla, Spain.
Frederick P RothLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Donnelly Centre and Department of Computer Science, University of Toronto, 160 College Street, Toronto M5S 3E1, Canada.
Daniel DurocherLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Electronic address: durocher@lunenfeld.ca.
Mount Sinai Hospital · CAInstituto de Biomedicina de Sevilla · ESThe Netherlands Cancer Institute · NL

Funding

Technology to understand genetic variant effects in contextRM1HG010461 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Bruce Colston Trapnell · 2019 to 2026
$18.9M
Molecular phenotyping of ~100,000 coding variants across Mendelian disease genesUM1HG011989 · NHGRI · DANA-FARBER CANCER INST · PI Marc Vidal · 2021 to 2026
$9.9M
NHGRI NIH HHS FDN159926NHGRI NIH HHS RM1 HG010461NHGRI NIH HHS UM1 HG011989
6 · The paper itself

Abstract

To maintain genome integrity, cells must accurately duplicate their genome and repair DNA lesions when they occur. To uncover genes that suppress DNA damage in human cells, we undertook flow-cytometry-based CRISPR-Cas9 screens that monitored DNA damage. We identified 160 genes whose mutation caused spontaneous DNA damage, a list enriched in essential genes, highlighting the importance of genomic integrity for cellular fitness. We also identified 227 genes whose mutation caused DNA damage in replication-perturbed cells. Among the genes characterized, we discovered that deoxyribose-phosphate aldolase DERA suppresses DNA damage caused by cytarabine (Ara-C) and that GNB1L, a gene implicated in 22q11.2 syndrome, promotes biogenesis of ATR and related phosphatidylinositol 3-kinase-related kinases (PIKKs). These results implicate defective PIKK biogenesis as a cause of some phenotypes associated with 22q11.2 syndrome. The phenotypic mapping of genes that suppress DNA damage therefore provides a rich resource to probe the cellular pathways that influence genome maintenance.

Indexed as

CRISPR-Cas SystemsDNA DamageDNA RepairHumansMutationPhenotypeATRcytarabineDNA damageDNA replication stressgenome stabilityTTT complex

Identifiers

PMID37478847
PMCPMC10530064
OpenAlexW4384938247

What OpenQuestion holds

Textmetadata
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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.