{"doi":"10.1126/sciadv.ade7997","title":"Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability","abstract":"Recent studies have described a DNA damage tolerance pathway choice that involves a competition between PrimPol-mediated repriming and fork reversal. Screening different translesion DNA synthesis (TLS) polymerases by the use of tools for their depletion, we identified a unique role of Pol ι in regulating such a pathway choice. Pol ι deficiency unleashes PrimPol-dependent repriming, which accelerates DNA replication in a pathway that is epistatic with ZRANB3 knockdown. In Pol ι-depleted cells, the excess participation of PrimPol in nascent DNA elongation reduces replication stress signals, but thereby also checkpoint activation in S phase, triggering chromosome instability in M phase. This TLS-independent function of Pol ι requires its PCNA-interacting but not its polymerase domain. Our findings unravel an unanticipated role of Pol ι in protecting the genome stability of cells from detrimental changes in DNA replication dynamics caused by PrimPol.","journal":"Science Advances","year":2023,"id":334491,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"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":1063297,"name":"Agostina P. Bertolin","orcid":null,"position":1,"is_corresponding":false},{"id":1062902,"name":"Sofía Venerus Arbilla","orcid":"0000-0003-2826-7615","position":2,"is_corresponding":false},{"id":1063298,"name":"Bryan A. Castaño","orcid":null,"position":3,"is_corresponding":false},{"id":1062903,"name":"Tiya Jahjah","orcid":"0000-0001-8065-7325","position":4,"is_corresponding":false},{"id":1062904,"name":"Jenny Kaur Singh","orcid":"0000-0001-7222-7317","position":5,"is_corresponding":false},{"id":1062905,"name":"Sebastián Omar Siri","orcid":"0000-0002-0945-5605","position":6,"is_corresponding":false},{"id":732655,"name":"María Victoria Castro","orcid":"0000-0002-2505-3120","position":7,"is_corresponding":false},{"id":1062906,"name":"María Belén de la Vega","orcid":"0009-0006-3775-9805","position":8,"is_corresponding":false},{"id":301611,"name":"Annabel Quinet","orcid":"0000-0003-0852-6181","position":9,"is_corresponding":false},{"id":1062907,"name":"Lisa Wiesmüller","orcid":"0000-0002-2397-5041","position":10,"is_corresponding":false},{"id":1062908,"name":"Vanesa Gottifredi","orcid":"0000-0001-9656-5951","position":11,"is_corresponding":false},{"id":1062901,"name":"Sabrina F. Mansilla","orcid":"0000-0001-7752-3377","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:09:48.843291Z","pmid":"37058556","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":[]}