RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination

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Abstract

Viral-induced DNA damage triggers both eukaryotic and prokaryotic innate immunity. Here, we report that self-DNA ends generated routinely during normal termination of bacterial replication suffice to trigger the P2-encoded OLD antiphage system. Normally, these physiological triggers are cleared by the dual helicase-nuclease activities of the conserved RecBCD enzyme, which acts as an immune safeguard analogous to mammalian TREX1 exonuclease and plant DBR1 debranching enzyme. However, when this clearance fails, the transient self-DNA ends persist and are recognized by ATP-bound OLD dimers via a positively charged channel across their ATPase subunits. ATP hydrolysis then activates OLD to cleave tRNAs, causing cytotoxicity. Single-cell microscopy reveals that dozens of OLD molecules associate with kilobases of adjacent DNA, amplifying the sparse physiological DNA end signal. Our findings reveal how an endogenous byproduct poses a constant autoimmune threat in bacteria, highlighting a universal molecular conflict across kingdoms and the convergent solutions evolved to resolve it.

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  1. Authors published a paper in Biorxiv, they used cutadapt in the study. Including #RRIDs will make this less ambiguous. SciScore made a table with this resource, see “Automated Services” module (download as csv, xml or #jats) #reproducibility #OpenScience

  2. RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination | bioRxiv

  3. www.biorxiv.org/content/10.6... New preprint from my lab revealing molecular conflicts between host replication and antiviral defense. RecBCD prevents this conflict by clearing immunogenic DNA ends produced during normal replication termination. #MicroSky #PhageSky

  4. RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination #SingleCell 🧪🧬🖥️ https://www.biorxiv.org/content/10.64898/2026.09.30.755081v1

  5. RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination https://www.biorxiv.org/content/10.64898/2026.09.30.755081v1

  6. RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination https://www.biorxiv.org/content/10.64898/2026.09.30.755081v1