{"doi":"10.1101/2022.02.24.481821","title":"Thymidine rescues ATR kinase inhibition induced deoxyuridine contamination in genomic DNA, cell death, and Type 1 interferon expression","abstract":"SUMMARY ATR kinase is a central regulator of the DNA damage response (DDR) and cell cycle checkpoints. ATR kinase inhibitors (ATRi’s) combine with radiation to generate CD8 + T cell-dependent responses in mouse models of cancer. We show that ATRi’s induce CDK1-dependent origin firing across active replicons in CD8 + T cells activated ex vivo while simultaneously decreasing the activity of rate-limiting enzymes for nucleotide biosynthesis. These pleiotropic effects of ATRi induce deoxyuridine (dU) contamination in genomic DNA, R loops, RNA-DNA polymerase collisions, and type-1 interferons (IFN-1). Remarkably, thymidine rescues ATRi-induced dU contamination, cell death, and IFN-1 expression in proliferating CD8 + T cells. Thymidine also rescues ATRi-induced cancer cell death. We propose that ATRi-induced dU contamination contributes to dose-limiting leukocytopenia and inflammation in the clinic and CD8 + T cell dependent anti-tumor responses in mouse models. We conclude that ATR is essential to limit dU contamination in genomic DNA and IFN-1 expression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302781,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":894707,"name":"Frank P. Vendetti","orcid":null,"position":1,"is_corresponding":false},{"id":894708,"name":"Andrew J. Cipriano","orcid":null,"position":2,"is_corresponding":false},{"id":894303,"name":"Pinakin Pandya","orcid":"0000-0002-1592-2388","position":3,"is_corresponding":false},{"id":894304,"name":"Joshua J. Deppas","orcid":"0000-0002-9093-7459","position":4,"is_corresponding":false},{"id":894305,"name":"Tatiana N. Moiseeva","orcid":"0000-0002-1181-9519","position":5,"is_corresponding":false},{"id":894709,"name":"Sandra Schamus-Haynes","orcid":null,"position":6,"is_corresponding":false},{"id":894306,"name":"Yiyang Wang","orcid":"0000-0001-9562-0621","position":7,"is_corresponding":false},{"id":694292,"name":"Drake Palmer","orcid":null,"position":8,"is_corresponding":false},{"id":625871,"name":"Hatice U. Osmanbeyoglu","orcid":"0000-0002-3175-1777","position":9,"is_corresponding":false},{"id":420722,"name":"Anna Bostwick","orcid":"0000-0001-5250-1788","position":10,"is_corresponding":false},{"id":237765,"name":"Nathaniel W. Snyder","orcid":"0000-0001-5643-8747","position":11,"is_corresponding":false},{"id":862229,"name":"Yi‐Nan Gong","orcid":"0000-0002-3643-4682","position":12,"is_corresponding":false},{"id":314761,"name":"Katherine M. Aird","orcid":"0000-0002-5828-2325","position":13,"is_corresponding":false},{"id":237079,"name":"Greg M. Delgoffe","orcid":"0000-0002-2957-8135","position":14,"is_corresponding":false},{"id":414176,"name":"Jan H. Beumer","orcid":"0000-0002-8978-9401","position":15,"is_corresponding":false},{"id":576133,"name":"Christopher J. Bakkenist","orcid":"0000-0001-9672-0886","position":16,"is_corresponding":false},{"id":894302,"name":"Norie Sugitani","orcid":"0000-0002-5582-8855","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:20.348385Z","pmid":null,"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":[]}