Discovery of a dual protease mechanism that promotes DNA damage checkpoint recovery.
Peter E BurbyZackary W SimmonsJeremy W SchroederLyle A SimmonsPublished in: PLoS genetics (2018)
The DNA damage response is a signaling pathway found throughout biology. In many bacteria the DNA damage checkpoint is enforced by inducing expression of a small, membrane bound inhibitor that delays cell division providing time to repair damaged chromosomes. How cells promote checkpoint recovery after sensing successful repair is unknown. By using a high-throughput, forward genetic screen, we identified two unrelated proteases, YlbL and CtpA, that promote DNA damage checkpoint recovery in Bacillus subtilis. Deletion of both proteases leads to accumulation of the checkpoint protein YneA. We show that DNA damage sensitivity and increased cell elongation in protease mutants depends on yneA. Further, expression of YneA in protease mutants was sufficient to inhibit cell proliferation. Finally, we show that both proteases interact with YneA and that one of the two proteases, CtpA, directly cleaves YneA in vitro. With these results, we report the mechanism for DNA damage checkpoint recovery in bacteria that use membrane bound cell division inhibitors.
Keyphrases
- dna damage
- dna repair
- high throughput
- single cell
- oxidative stress
- dna damage response
- cell proliferation
- cell therapy
- signaling pathway
- poor prognosis
- induced apoptosis
- bacillus subtilis
- cell cycle
- binding protein
- small molecule
- stem cells
- epithelial mesenchymal transition
- cell cycle arrest
- genome wide
- dna methylation
- amino acid
- long non coding rna
- bone marrow
- cord blood
- mesenchymal stem cells