A DNA damage-induced, SOS-independent checkpoint regulates cell division in Caulobacter crescentus.

Abstract

Author SummaryCells have evolved sophisticated mechanisms for repairing their DNA and maintaining genome integrity. A critical aspect of the repair process is an arrest of cell cycle progression, thereby ensuring that cell division is not attempted before the genome has been repaired and fully duplicated. Our paper explores the molecular mechanisms that underlie the inhibition of cell division following DNA damage in the bacterium Caulobacter crescentus. For most bacteria, the primary, and only mechanism previously described involves the SOS response, in which DNA damage induces cleavage of the transcriptional repressor LexA, driving induction of a battery of genes that includes an inhibitor of cell division (sulA in E. coli and sidA in Caulobacter). Here, we report that Caulobacter cells have a second, SOS-independent damage response pathway that induces another division inhibitor, didA, which works together with sidA to block cell division following DNA damage. We also identify the damage-sensitive transcription factor responsible for inducing DidA. Finally, our study demonstrates that DidA and SidA inhibit cell division in an atypical manner. Many division inhibitors in bacteria appear to inhibit the protein FtsZ, which forms a ring at the site of cell division. DidA and SidA, however, target a trio of proteins, FtsW/I/N, that help synthesize the new cell wall that will separate the daughter cells (the septum). In sum, our work expands our understanding of how bacterial cells respond to DNA damage and the mechanisms by which they regulate cell division.