Uncovering the effects of non-lethal oxidative stress on replication initiation in Escherichia coli

• Published in: Gene Vol. 933; p. 148992
• Main Authors: Qiao, Jiaxin, Du, Dongdong, Wang, Yao, Xi, Lingjun, Zhu, Weiwei, Morigen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2025
• Subjects: AAA+ proteases; Antioxidant enzymes; Base excision repair; DNA replication initiation; Hydrogen peroxide; Non-lethal oxidative stress; DNA replication initiation; NAC; A.O; CAA; Hydrogen peroxide; CFU; Antioxidant enzymes; ROS; AAA+ proteases; D.T; Non-lethal oxidative stress; Base excision repair
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2024.148992

•Exogenous non-lethal H2O2 suppresses DNA replication initiation in E. coli.•Deletion of antioxidant enzymes cause a delayed replication initiation.•MutY contributes to replication initiation during H2O2 stress.•AAA+ proteases are involved in the effect of oxidative stress on replication initiation. Cell cycle adaptability assists bacteria in response to adverse stress. The effect of oxidative stress on replication initiation in Escherichia coli remains unclear. This work examined the impact of exogenous oxidant and genetic mutation-mediated oxidative stress on replication initiation. We found that 0–0.5 mM H2O2 suppresses E. coli replication initiation in a concentration-dependent manner but does not lead to cell death. Deletion of antioxidant enzymes SodA-SodB, KatE, or AhpC results in delayed replication initiation. The antioxidant N-acetylcysteine (NAC) promotes replication initiation in ΔkatE and ΔsodAΔsodB mutants. We then explored the factors that mediate the inhibition of replication initiation by oxidative stress. MutY, a base excision repair DNA glycosylase, resists inhibition of replication initiation by H2O2. Lon protease deficiency eliminates inhibition of replication initiation mediated by exogenous H2O2 exposure but not by katE or sodA-sodB deletion. The absence of clpP and hslV further delays replication initiation in the ΔktaE mutant, whereas hflK deletion promotes replication initiation in the ΔkatE and ΔsodAΔsodB mutants. In conclusion, non-lethal oxidative stress inhibits replication initiation, and AAA+ proteases are involved and show flexible regulation in E. coli.