Redox controls RecA protein activity via reversible oxidation of its methionine residues

Reactive oxygen species (ROS) cause damage to DNA and proteins. The RecA protein plays a central role in the bacterial response to DNA damage. Here we report that RecA itself is also targeted by ROS. In vivo consequences of RecA oxidation include defects in SOS induction, DNA repair efficiency, and P1 transduction. In vitro, oxidized RecA fails to display ATPase activity, DNA strand exchange capacity and formation of nucleofilaments. Consistently, mass spectrometry analysis of oxidized RecA revealed that four out of 9 Met residues have been converted to methionine sulfoxide (Met-O). Specifically, mimicking the oxidation of Met35 by changing it for Gln caused complete loss of function whereas mimicking oxidation of Met164 resulted in constitutive SOS activation and loss of recombination activity. The harmful effects of oxidation of RecA were mitigated by repairing activities of methionine sulfoxide reductases MsrA and MsrB, which suppressed all ROS-induced modifications of RecA activity....