{"doi":"10.1016/j.molcel.2023.06.025","title":"Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens","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.","journal":"Molecular Cell","year":2023,"id":336435,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9412,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1066857,"name":"Daniel Tabet","orcid":"0009-0006-5480-7733","position":1,"is_corresponding":false},{"id":1066858,"name":"Diana Rubio-Contreras","orcid":"0000-0003-4828-4906","position":2,"is_corresponding":false},{"id":1066859,"name":"Linjiang Lao","orcid":"0000-0001-6862-9903","position":3,"is_corresponding":false},{"id":1066860,"name":"Arne Nedergaard Kousholt","orcid":"0000-0002-3972-1740","position":4,"is_corresponding":false},{"id":297962,"name":"Jochen Weile","orcid":"0000-0003-1628-9390","position":5,"is_corresponding":false},{"id":229261,"name":"Henrique Melo","orcid":null,"position":6,"is_corresponding":false},{"id":1066861,"name":"Lisa Hoeg","orcid":"0000-0002-0109-3646","position":7,"is_corresponding":false},{"id":229264,"name":"Sumin Feng","orcid":null,"position":8,"is_corresponding":false},{"id":106211,"name":"Atina G. Coté","orcid":"0000-0002-0340-9325","position":9,"is_corresponding":false},{"id":576637,"name":"Zhen‐Yuan Lin","orcid":null,"position":10,"is_corresponding":false},{"id":271494,"name":"Dheva Setiaputra","orcid":"0000-0003-2956-6422","position":11,"is_corresponding":false},{"id":13624,"name":"Jos Jonkers","orcid":"0000-0002-9264-9792","position":12,"is_corresponding":false},{"id":44860,"name":"Anne‐Claude Gingras","orcid":"0000-0002-6090-4437","position":13,"is_corresponding":false},{"id":1066862,"name":"Fernando Gómez-Herreros","orcid":"0000-0002-5693-3489","position":14,"is_corresponding":false},{"id":106276,"name":"Frederick P. Roth","orcid":"0000-0002-6628-649X","position":15,"is_corresponding":false},{"id":94095,"name":"Daniel Durocher","orcid":"0000-0003-3863-8635","position":16,"is_corresponding":false},{"id":626481,"name":"Yichao Zhao","orcid":"0000-0001-8784-5361","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:17.243221Z","pmid":"37478847","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}