{"doi":"10.1093/nar/gkaf540","title":"PglZ from Type I BREX phage defence systems is a metal-dependent nuclease that forms a sub-complex with BrxB","abstract":"BREX (Bacteriophage Exclusion) systems, identified through shared identity with Pgl (Phage Growth Limitation) systems, are a widespread, highly diverse group of phage defence systems found throughout bacteria and archaea. The varied BREX Types harbour multiple protein subunits (between four and eight) and all encode a conserved putative phosphatase, PglZ, and an equally conserved, putative ATPase, BrxC. Almost all BREX systems also contain a site-specific methyltransferase, PglX. Despite having determined the structure and fundamental biophysical and biochemical behaviours of several BREX factors (including the PglX methyltransferase, the BrxL effector, the BrxA DNA-binding protein, and a commonly-associated transcriptional regulator, BrxR), the mechanism by which BREX impedes phage replication remains largely undetermined. In this study, we identified a stable BREX sub-complex of PglZ:BrxB, generated and validated a structural model of that protein complex, and assessed the biochemical activity of PglZ from BREX, revealing it to be a metal-dependent nuclease. PglZ can cleave cyclic oligonucleotides, linear oligonucleotides, plasmid DNA and both non-modified and modified linear phage genomes. PglZ nuclease activity has no obvious role in BREX-dependent methylation, but does contribute to BREX phage defence. BrxB binding does not impact PglZ nuclease activity. These data contribute to our growing understanding of BREX phage defence.","journal":"Nucleic Acids Research","year":2025,"id":515151,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"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":678189,"name":"Lindsey Doyle","orcid":"0000-0002-0008-473X","position":1,"is_corresponding":false},{"id":39087,"name":"Maria Puiu","orcid":"0000-0002-4078-2831","position":2,"is_corresponding":false},{"id":1378693,"name":"Abigail Kelly","orcid":"0000-0003-0818-912X","position":3,"is_corresponding":false},{"id":1187856,"name":"Andrew Nelson","orcid":"0000-0001-6665-4929","position":4,"is_corresponding":false},{"id":1379375,"name":"Alex Kaiser","orcid":null,"position":5,"is_corresponding":false},{"id":1379376,"name":"Sydney McGuire","orcid":null,"position":6,"is_corresponding":false},{"id":1379377,"name":"Julieta Peralta Acosta","orcid":null,"position":7,"is_corresponding":false},{"id":103745,"name":"Darren Smith","orcid":"0000-0003-4925-467X","position":8,"is_corresponding":false},{"id":861972,"name":"Barry L Stoddard","orcid":"0000-0001-5174-7858","position":9,"is_corresponding":false},{"id":560047,"name":"Brett K. Kaiser","orcid":null,"position":10,"is_corresponding":false},{"id":1084863,"name":"Tim R. Blower","orcid":"0000-0002-7390-6458","position":11,"is_corresponding":false},{"id":1378692,"name":"Jennifer J. Readshaw","orcid":"0009-0007-5734-1470","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:48:34.431522Z","pmid":"40548935","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":[]}