In Escherichia coli, the adenine residues at GATC sequences are methylated at the 6 position by a DNA adenine methylase (Dam). Immediately after replication, the new strand is unmethylated. Mispairs are recognized by the MutS protein, which then recruits the MutL and MutH functions. MutH cuts the hemimethylated DNA, on the unmethylated strand, and ultimately the mismatched base is excised, and the gap is filled in and ligated. E. coli dam strains, deficient in DNA methylation, have an active but non-directed MMRS that can cause cell death by making double-strand breaks (DSBs) on unmethylated GATC sequences . Here we show that increasing the level of MutS, -L or -H in E. coli dam cells enhances the mismatch-stimulating killing effect resulting in strains with an apparent reduced mutation frequency. However, these strains have a similar duplication time, percentage of live/dead cells and morphotype to that of the dam strain. These strains also showed an increased sensitivity to the base analogue 2-AP, confirming that they have an improved MMRS. These results let us predict that successive cultures of dam cells could be enriched in cells with an improved MMRS. Preliminary results confirms this hypothesis that could be one important factor to understand why while mutH, mutL and mutS strains of E. coli confer a marked selective advantage in competition with otherwise isogenic wild-type strains, dam strains are negatively selected.