Escherichia coli MutS, MutL and MutH proteins act sequentially in the mismatch repair system (MMRS), which repairs DNA replication errors. We have previously shown that mutL from Pseudomonas aeruginosa complements an E. coli MutL-deficient strain. The analysis of the amino acids sequences, the E. coli MutL and MutH crystal structure and the interaction between MutL and MutH mutant proteins or protein segments lets us identify amino acids that could be important for MutL-MutH interaction. We wanted to use the same strategy to analyze MutS-MutL interaction, however P. aeruginosa MutS, although being more homologue to E. coli MutS protein (63% identical) than the MutL protein (50% identical), not only does not complement an E. coli MutS-deficient strain, but it also produces a dominant-negative effect on an E. coli MMRS-proficient strain increasing the mutation frequency by 50-fold. Using N-terminal His-tagged MutS proteins we observed that P. aeruginosa MutS protein is highly degraded in E. coli cells. In order to determine whether N- or C-terminal fragments could be generated and be responsible for the dominant-negative effect, a C- and N-terminal His-tagged P. aeruginosa MutS protein was constructed and experiments are under development.