The DR2416/DR2415 two-component system is responsible for the radioresistance of Deinococcus radiodurans.

Two-component system (TCS) plays a crucial role in translating stimulus signals into specific adaptive responses and aids prokaryotic organisms in withstanding diverse stresses. Deinococcus radiodurans is renowned for its exceptional radioresistance and has become a valuable model for studying DNA repair, bioremediation and planetary protection space missions. TCSs are well-developed by this bacterium, thus the role in its radioresistance can be envisaged. DR2416 was predicted to be a histidine kinase, and DR2415, a response regulator. Our study revealed that deleting dr2416 or (and) dr2415 reduced D. radiodurans' resistance to various DNA damage agents, including ionizing radiation, hydrogen peroxide, and mitomycin C. The DR2416 protein was situated on the membrane of D. radiodurans. Western blotting analysis revealed that DR2415 was significantly induced by ionizing radiation. The Phos-tag SDS-PAGE assay illustrated that DR2416 could undergo self-phosphorylation at His259 in vitro and subsequently transfer the phosphoryl group to the Asp52 residue of DR2415. The qRT-PCR method showed that the DR2416/DR2415 TCS regulated genes related to DNA double-strand break repair and reactive oxygen species (ROS) removal, including recN (dr1477), sbcC (dr1922), and katE (dra0259). In conclusion, our findings suggested that the DR2416/DR2415 TCS might provide radioresistance to D. radiodurans through DNA damage repair and ROS scavenging mechanisms.