307: SNIPE membrane nuclease cleaves phage λ DNA during ManYZ-mediated genome injection in Escherichia coli

Saxton DS et al., Nature, doi:10.1038/s41586-026-10207-1 - In E. coli, the membrane-bound nuclease SNIPE directly cleaves incoming phage λ DNA during genome injection, blocking infection via ManYZ and tape-measure protein interactions. Key terms: SNIPE, GIY-YIG nuclease, lambda phage, ManYZ, tape measure protein. Study Highlights:In Escherichia coli, the membrane-anchored protein SNIPE was shown to block phage λ by directly cleaving DNA during genome injection. The authors combined radiolabelled 32P phage DNA assays, time-lapse CFP-ParB/ParS microscopy, TurboID proximity labelling and pBPA crosslinking to map SNIPE localization and interactions. They report that membrane-localized SNIPE requires a DUF4041 domain and a GIY-YIG nuclease domain to generate DNA fragments during injection, reducing CFP-ParB puncta ~30-fold and producing a smear of 32P-labelled fragments; an E414A nuclease mutant abolished activity. Functionally, SNIPE prevents λ replication and cell lysis and provides broad defence against many siphoviruses via interactions with ManYZ and phage tape-measure proteins. Conclusion:SNIPE is a membrane-localized bacterial defence protein that associates with ManYZ and phage tape-measure proteins to directly cleave incoming phage DNA during genome injection, thereby blocking infection. Music:Enjoy the music based on this article at the end of the episode. Article title:A membrane-bound nuclease directly cleaves phage DNA during genome injection First author:Saxton DS Journal:Nature, doi:10.1038/s41586-026-10207-1 DOI:10.1038/s41586-026-10207-1 Reference:Saxton DS, DeWeirdt PC, Doering CR, Roney IJ & Laub MT. A membrane-bound nuclease directly cleaves phage DNA during genome injection. Nature. 2026. https://doi.org/10.1038/s41586-026-10207-1 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/snipe-membrane-nuclease-phage-injection QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-03-04. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited transcript sections covering SNIPE architecture and membrane localization, autoinhibition, phage DNA cleavage during genome injection (Hershey–Chase style), interactions with ManYZ andTape-measure proteins (TMP), proximity labelling, Bas14 mutation experiments, and SNIPE homologues/evolution.- transcript topics: SNIPE membrane localization and domain architecture; Autoinhibition and self-DNA protection at the membrane; Cleavage of phage DNA during genome injection and Hershey–Chase-like evidence; Interaction with ManYZ and phage tape-measure protein during infection; TurboID proximity labelling findings for ManYZ and TMP interactions; Broad siphovirus defense and Bas14 mutation findings QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 7- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- SNIPE is a membrane-anchored protein with an N-terminal transmembrane domain, a DUF4041 domain in the middle, and a GIY-YIG nuclease domain at the C...