Artículo
Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens
Autor/es | Zhao, Yichao
Tabet, Daniel Rubio Contreras, Diana Lao, Linjiang Kousholt, Arne Nedergaard Weile, Jochen Gómez Herreros, Fernando Durocher, Daniel |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2023-08-03 |
Fecha de depósito | 2024-05-17 |
Publicado en |
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Resumen | 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 ... 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 |
Agencias financiadoras | National Institutes of Health (NIH). Estados Unidos Canadian Cancer Society. Canada Canadian Institutes of Health Research CIHR |
Identificador del proyecto | RM1HG010461
UM1HG011989 705644 PJT-180438 FDN159926 |
Cita | Zhao, Y., Tabet, D., Rubio Contreras, D., Lao, L., Kousholt, A.N., Weile, J.,...,Durocher, D. (2023). Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens. Molecular Cell, 83 (15), 2792-2809. https://doi.org/10.1016/j.molcel.2023.06.025. |
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