Fig. 5.

How eATL interferes with MMR-mediated processing of O⁶-alkylG:T replication intermediates. eATL binds to O⁶-alkylguanine-containing oligonucleotides and thus inhibits MutS protein binding to the G*:T mispair. As a consequence, eATL prevents MMR-mediated processing of the G*:T replication intermediates. Data presented in the present paper show that MMR-mediated toxicity involves MutH functions rather than just MutS binding and suggest that repeated cycles of processing trigger toxicity in E. coli. The effect of eATL is observed for the larger O⁶-alkylG adducts (hydroxyethyl and hydroxypropyl) but not for methyl, in good agreement with the respective binding affinities of eATL for the different adducts.