Hallmarks of DNA replication stress responses in <i>Escherichia coli</i> and <i>Bacillus subtilis</i>

Escherichia coli and Bacillus subtilis provide well-studied models for understanding how bacteria manage DNA replication stress (RS). These bacteria employ various strategies to detect and stabilize stalled replication forks (RFs), circumvent or bypass lesions, resolve replication-transcription conflicts (RTCs), and resume replication. While central features of responses to RS are broadly conserved, distinct mechanisms have evolved to adapt to their complex environments. In this review, we compare the RS sensors, regulators, and molecular players of these two phylogenetically distant bacteria. The differing roles of the RecA recombinase are used as the touchstone of the distinct strategies each bacterium employs to overcome RS, provided that the fork does not collapse. In E. coli, RecA mainly assembles at locations distal from replisomes, promotes global responses, and contributes to circumvent or bypass lesions. RecA assembles less frequently at stalled RFs, and its role in lesion skipping, fork remodeling, RTC resolution, and replication restart remains poorly defined. In contrast, in B. subtilis, RecA assembles at stalled forks, fine-tunes damage signaling, and, in concert with RecA-interacting proteins, may facilitate fork remodeling or lesion bypass, overcome RTCs, and contribute to replication restart.