Transcription-replication collisions trigger high-fidelity replication reset.

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 da

SUBMITTER: Cooke MB 

PROVIDER: S-EPMC12651559 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature