Effect of xthA deletion in the activation of the E. coli SOS response by gamma rays, UV-C light and other genotoxic agents.

The SOS response contains a set of about 45 genes related to the repair or tolerance to DNA damage. These genes are normally blocked but when lesions upon the genetic material occur an SOS signal is generated allowing their expression. Most types of DNA lesions must be modified or processed to induce SOS. In a previous work, a model was proposed suggesting the possible paths that could be followed from the different types of lesions to the induction of the response. One of these possible routes is through the base excision repair mechanism (BER). Since in E. coli the AP endonuclease exonuclease III plays a key role in this repair pathway, in the present study we evaluate the participation of xthA product in the processing of DNA lesions made by gamma rays, UV-C light, ethyl methanesulphonate, methyl methanesulphonate, mitomycin C, hydrogen peroxide and tert-buthylhydroperoxide to trigger the SOS response. A strain defective in xthA and a wt strain were exposed to different genotoxic agents and survival and SOS induction were analyzed. The results show differences in the survival and SOS induction to each genotoxic agent between the wt strain and the xthA mutant; depending on the type of DNA damage inflicted, the SOS response level was either higher or lower compared to the wt strain. This suggests that while the AP endonuclease role of exonuclease III enzyme suppresses SOS induction when bulky and methylated lesions occur, it enhances SOS induction when the damage is generated by ROS, in agreement with a previously proposed model.