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

© 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Detalles Bibliográficos
Autores: Zhao, Yichao, Tabet, Daniel, Rubio-Contreras, Diana, Lao, Linjiang, Kousholt, Arne Nedergaard, Weile, Jochen, Melo, Henrique, Hoeg, Lisa, Feng, Sumin, Coté, Atina G., Lin, Zhen-Yuan, Setiaputra, Dheva, Jonkers, Jos, Gingras, Anne-Claude, Gómez-Herreros, Fernando, Roth, Frederick P., Durocher, Daniel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/350597
Acceso en línea:http://hdl.handle.net/10261/350597
Access Level:acceso abierto
Palabra clave:DNA damage
Genome stability
DNA replication stress
Cytarabine
ATR
TTT complex
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spelling Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screensZhao, YichaoTabet, DanielRubio-Contreras, DianaLao, LinjiangKousholt, Arne NedergaardWeile, JochenMelo, HenriqueHoeg, LisaFeng, SuminCoté, Atina G.Lin, Zhen-YuanSetiaputra, DhevaJonkers, JosGingras, Anne-ClaudeGómez-Herreros, FernandoRoth, Frederick P.Durocher, DanielDNA damageGenome stabilityDNA replication stressCytarabineATRTTT complex© 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).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.This work was supported by grants from NIH (RM1HG010461 and UM1HG011989, to F.P.R.), from the Canadian Cancer Society (705644 to D.D.), and from the Canadian Institutes of Health Research (CIHR, grants PJT-180438 to D.D. and FDN159926 to F.P.R.).Peer reviewedCell PressNational Institutes of Health (US)Canadian Cancer SocietyCanadian Institutes of Health ResearchConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/350597reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1016/j.molcel.2023.06.025Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3505972026-05-22T06:33:51Z
dc.title.none.fl_str_mv Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
title Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
spellingShingle Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
Zhao, Yichao
DNA damage
Genome stability
DNA replication stress
Cytarabine
ATR
TTT complex
title_short Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
title_full Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
title_fullStr Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
title_full_unstemmed Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
title_sort Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
dc.creator.none.fl_str_mv Zhao, Yichao
Tabet, Daniel
Rubio-Contreras, Diana
Lao, Linjiang
Kousholt, Arne Nedergaard
Weile, Jochen
Melo, Henrique
Hoeg, Lisa
Feng, Sumin
Coté, Atina G.
Lin, Zhen-Yuan
Setiaputra, Dheva
Jonkers, Jos
Gingras, Anne-Claude
Gómez-Herreros, Fernando
Roth, Frederick P.
Durocher, Daniel
author Zhao, Yichao
author_facet Zhao, Yichao
Tabet, Daniel
Rubio-Contreras, Diana
Lao, Linjiang
Kousholt, Arne Nedergaard
Weile, Jochen
Melo, Henrique
Hoeg, Lisa
Feng, Sumin
Coté, Atina G.
Lin, Zhen-Yuan
Setiaputra, Dheva
Jonkers, Jos
Gingras, Anne-Claude
Gómez-Herreros, Fernando
Roth, Frederick P.
Durocher, Daniel
author_role author
author2 Tabet, Daniel
Rubio-Contreras, Diana
Lao, Linjiang
Kousholt, Arne Nedergaard
Weile, Jochen
Melo, Henrique
Hoeg, Lisa
Feng, Sumin
Coté, Atina G.
Lin, Zhen-Yuan
Setiaputra, Dheva
Jonkers, Jos
Gingras, Anne-Claude
Gómez-Herreros, Fernando
Roth, Frederick P.
Durocher, Daniel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv National Institutes of Health (US)
Canadian Cancer Society
Canadian Institutes of Health Research
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv DNA damage
Genome stability
DNA replication stress
Cytarabine
ATR
TTT complex
topic DNA damage
Genome stability
DNA replication stress
Cytarabine
ATR
TTT complex
description © 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/350597
url http://hdl.handle.net/10261/350597
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1016/j.molcel.2023.06.025
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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