A positive feedback loop between NPR1 and SOG1 reinforces genotoxic tolerance in Arabidopsis

Cellular functions and viability of living organisms are constantly challenged by endogenous and environmental agents that can cause DNA damage. In plants, application of DNA-damaging agents, such as salicylic acid (SA) and the double-strand break-inducing antibiotic Zeocin, triggers the DNA damage response, thus inducing genotoxic tolerance. We found that the SA-responsive gene NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) and the DNA damage-responsive gene SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1) are both essential for genotoxic tolerance. Mutants lacking either NPR1 or SOG1 exhibited reduced tolerance to genotoxic stress. Furthermore, NPR1 and SOG1 formed a positive feedback loop at the transcriptional level, which amplified genotoxic responses. Additionally, NPR1 and SOG1 physically interacted with each other and showed co-binding to the NAC085 gene promoter, synergistically activating its expression and consequently inducing genotoxic tolerance. Genetic analysis revealed that NAC085 acts downstream of NPR1 and SOG1 to control genotoxic tolerance. Taken together, our results demonstrate that a positive feedback loop between NPR1 and SOG1 promotes NAC085 expression, thereby enhancing genotoxic tolerance and safeguarding genome integrity in plants.