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

• Published in: PLoS biology Vol. 12; no. 10; p. e1001977
• Main Authors: Modell, Joshua W, Kambara, Tracy K, Perchuk, Barrett S, Laub, Michael T
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2014; Public Library of Science (PLoS)
• Subjects: Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biology and Life Sciences; Caulobacter crescentus - physiology; Cell cycle; Cell Cycle Checkpoints; Cell Division; Chromosomes; Deoxyribonucleic acid; DNA; DNA Damage; Genomes; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microscopy; Mutation, Missense; Plasmids; Proteins; Studies; Suppression, Genetic; Transcription factors; Transcription Factors - metabolism
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1001977

Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage.