RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination
- 1New England Biolabs
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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BibTeX
@misc{govande2026recbcd,
title = {{RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination}},
author = {A. A. Govande and B. Ramsey and I. Unlu and S. K. Amundsen and T. A. Nagy and A. Hassan and M. Smiley and C. Trautman and A. T. Whiteley and G. R. Smith and S. Kim and H. C. Lim},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755081},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755081v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination
AU - A. A. Govande
AU - B. Ramsey
AU - I. Unlu
AU - S. K. Amundsen
AU - T. A. Nagy
AU - A. Hassan
AU - M. Smiley
AU - C. Trautman
AU - A. T. Whiteley
AU - G. R. Smith
AU - S. Kim
AU - H. C. Lim
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755081
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755081v1
AB - 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.
ER -