![]() Furthermore, an in-depth analysis allowed us to show that Met residues are not all oxidized at the same rate, and that functional consequences of oxidation depend upon which Met residue is being hit. We show that MsrA/B are able to rescue oxidized RecA activities. We report that RecA is targeted by ROS and this abrogates both RecA recombination and SOS induction capacities. RecA promotes DNA recombination and coordinates stress response by inducing the expression of the SOS regulatory system. In this study, we identified the ubiquitous recombinase RecA as a substrate of MsrA/B. However, a molecular understanding of the contribution of Msr as an anti-ROS defense needs the actual identification of proteins, whose activities are hampered by oxidation and can be rescued by Msr’s repairing activity. Global proteomic or dedicated studies identified substrates, like the ubiquitous protein SRP54 ( Ezraty et al., 2004 Gennaris et al., 2015) and several other proteins listed in the database MetOSite ( ) ( Valverde et al., 2019). Lack of functional MsrA/B yielded to pleiotropic phenotypes related to bacterial virulence or aging. Consequently, full repair of a given cytosolic oxidized protein requires the action of both MsrA and MsrB ( Tsvetkov et al., 2005). MsrA and MsrB have a strict stereospecificity for their substrates, with MsrA reducing only Met- S-SO and MsrB reducing only Met- R-SO diastereoisomers. In prokaryotes, MsrA and MsrB are mostly present in the cytoplasm ( Ezraty et al., 2017 Dos et al., 2018). Thioredoxin/glutaredoxin reductases can reduce oxidized cysteinyl while methionine sulfoxide reductase (Msr) reduces methionine sulfoxide residues (Met-O). These post-translational oxidations can be reversed by dedicated protein repair pathways present in all domains of life. Within proteins, sulfur-containing cysteinyl and methionyl residues can be oxidized to sulfenic acid adducts and methionine sulfoxide, respectively ( Ezraty et al., 2017). Exposure to ROS creates enough damage to impair cellular homeostasis in all living systems ( Imlay, 2015). ROS are extremely harmful for the cell, leading to nucleic acid damages, protein oxidation, and lipid peroxidation. Besides the endogenous production, ROS arises from various external sources such as metal, UV radiation, or pathogen defenses ( Imlay, 2019). Aerobic metabolism produces reactive oxygen species (ROS) such as superoxide (O 2° -), hydroxyl radicals (HO°), and the non-radical molecule hydrogen peroxide (H 2O 2). ![]()
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