Abstract
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.
Highlights
The DNA damage response (DDR, SOS response in bacteria) is an important pathway for maintaining genome integrity in all domains of life
We present a model of DNA damage checkpoint recovery for bacteria that use the more wide-spread mechanism employing a small, membrane bound cell division inhibitor
We reasoned that the combined data would provide a collection of genes that are generally important for the DNA damage response
Summary
The DNA damage response (DDR, SOS response in bacteria) is an important pathway for maintaining genome integrity in all domains of life. Misregulation of the DDR in humans can result in various disease conditions [1, 2], and in bacteria the SOS response has been found to be important for survival under many stressors [3,4,5]. The DNA damage response in all organisms results in three principle outcomes: a transcriptional response, which can vary depending on the type of DNA damage incurred, DNA repair, and activation of a DNA damage checkpoint [6,7,8,9]. The SOS-dependent DNA damage checkpoint relies on expression of a cell division inhibitor, though the type of inhibitor varies between bacterial species
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