Language
English
Publication Date
11-26-2025
Journal
Nucleic Acids Research
DOI
10.1093/nar/gkaf1227
PMID
41297800
PMCID
PMC12651559
PubMedCentral® Posted Date
11-26-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Double-stranded DNA ends arise from external agents or cellular processes like transcription-replication collisions (TRCs), threatening genome stability. Here, we performed genomic CRISPRi screens to uncover DNA end formation factors in Escherichia coli. We discovered that translation-transcription decoupling causes DNA end formation through a TRC-dependent pathway, which is lethal when DNA end processing by RecBCD is disrupted, but not when recombination is disrupted. We find that TRCs cause replisome stalling followed by "rear-ending" from trailing replisomes which generates free DNA ends, rather than strand breaks. Surprisingly, these DNA ends are resolved through a process we call "replication reset", where the stalled replicore is degraded, without triggering recombination, the DNA damage response, or mutagenesis. This hidden replicore-degradation resets the replication cycle without consequence for the genome. This discovery reveals a novel DNA safeguard mechanism for preserving genome stability when replication is disturbed and challenges the notion that TRCs necessarily cause genome instability in bacteria.
Keywords
DNA Replication, Escherichia coli, Transcription, Genetic, Genomic Instability, DNA, Bacterial, Escherichia coli Proteins, Exodeoxyribonuclease V, DNA Damage
Published Open-Access
yes
Recommended Citation
Cooke, Matthew B; Welch, Kobie T; Deus Ramirez, Laura; et al., "Transcription-Replication Collisions Trigger High-Fidelity Replication Reset" (2025). Faculty and Staff Publications. 5045.
https://digitalcommons.library.tmc.edu/baylor_docs/5045
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons