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/

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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-terminus.
- SNIPE autoinhibits its nuclease activity when anchored to the inner membrane to avoid autoimmune DNA cleavage.
- SNIPE cleaves phage DNA during genome injection, producing fragmented 32P DNA signals and reducing infection.
- CFP-ParB foci (parS-labelled phage DNA) are reduced by ~30-fold in SNIPE-expressing cells during λparS infection.
- A Hershey–Chase–style assay shows a smear of 32P-labelled DNA fragments in SNIPE-expressing cells, reversed by nuclease-inactive mutants (E414A).
- SNIPE associates with ManYZ before infection and with phage tape-measure proteins during genome injection.

QC result: Pass.