{"doi":"10.1126/science.aea8769","title":"Recurrent acquisition of nuclease-protease pairs in antiviral immunity","abstract":"Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin-like protease repeatedly acquired by multiple, otherwise unrelated antiviral immune systems in bacteria. Cell-based and biochemical assays revealed that the nuclease is a proenzyme that cleaves DNA only after activation by its partner protease. Two distinct immune systems, Hachiman and AVAST (antiviral adenosine triphosphatase/nucleoside triphosphatase of the STAND superfamily, Avs), use the same mechanism of proteolytic activation despite their independent evolutionary origins. Examination of nuclease-protease inheritance patterns identified caspase-nuclease ( canu ) genomic loci that confer antiviral defense in a pathway reminiscent of eukaryotic caspase activation. These results uncover the coordinated activities of pronucleases and their activating proteases within different immune systems and show how coevolution enables defense system innovation.","journal":"Science","year":2025,"id":533068,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":906967,"name":"Jason J. Hu","orcid":"0000-0002-1103-2177","position":1,"is_corresponding":false},{"id":806785,"name":"Santiago C. Lopez","orcid":"0000-0001-7576-2438","position":2,"is_corresponding":false},{"id":556964,"name":"Benjamin A. Adler","orcid":"0000-0002-7488-3040","position":3,"is_corresponding":false},{"id":1414583,"name":"Claire E O'Brien","orcid":"0009-0002-9782-2846","position":4,"is_corresponding":false},{"id":1371282,"name":"K.‐H. HSIEH","orcid":null,"position":5,"is_corresponding":false},{"id":1414584,"name":"C. A. Meredith","orcid":"0009-0002-4597-3239","position":6,"is_corresponding":false},{"id":1038373,"name":"Kenneth J. Loi","orcid":"0009-0009-5508-6511","position":7,"is_corresponding":false},{"id":1037831,"name":"Peter H. Yoon","orcid":"0000-0002-9156-1393","position":8,"is_corresponding":false},{"id":504306,"name":"Erin Doherty","orcid":"0000-0002-1555-4124","position":9,"is_corresponding":false},{"id":1037837,"name":"Arushi Lahiri","orcid":"0000-0001-6834-4692","position":10,"is_corresponding":false},{"id":2407,"name":"Jennifer A. Doudna","orcid":"0000-0001-9161-999X","position":11,"is_corresponding":false},{"id":348596,"name":"Owen T. Tuck","orcid":"0000-0002-0348-6910","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T02:51:27.893975Z","pmid":"41231971","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":[]}