The mismatch repair (MMR) system is essential to all organisms because it maintains the stability of gene during repeated duplication. Mistakes that escape these fidelity devices are corrected by mismatch repair, further elevating fidelity 50-1000-fold. Inactivation of the human mismatch repair system is the cause of hereditary nonpolyposis colon cancer (HNPCC) and has been implicated in the development of a subset of sporadic tumors that occur in a variety of tissues. Various functions, in addition to mismatch repair during replication, have been reported for MMR proteins such as promotion of meiotic crossover, DNA damage surveillance and diversification of immunoglobulins.Mismatch repair and DNA replication are highly associated. Our work mainly focused on coordinated functions of DNA polymerase III in E.coli DNA mismatch repair. In an effort to better understand the relationship between these 2 systems, the potential interactions between the Escherichia coli MMR protein and the clamp loader subunits of E. coli DNA polymerase III were analyzed by far western blotting and then confirmed and characterized by surface plasmon resonance (SPR) imaging. The results showed that the MMR key protein MutL could directly interact with both the individual subunitsδ,δ' andγand the complex of these subunits (clamp loader). Kinetic parameters revealed that the interactions are strong and stable,suggesting that MutL might be involved in the recruitment of the clamp loader during the resynthesis step in MMR. The interactions between MutL, theδandγsubunits, and the clamp loader were observed to be modulated by ATP. Deletion analysis demonstrated that both the N-terminal residues (1-293) and C-terminal residues (556-613) of MutL are required for interacting with the subunitsδandδ' Based on these findings and the available information, the network of interactions between the MMR components and the DNA polymerase III subunits was established; this network provides strong evidence to support the notion that DNA replicationExcept for the newly found interactions, we study the biological significance of interaction between MutS andβclamp(one of the subunits of DNA polymerase III ).We found thatβclamp binding site located in the MutS N-or C-terminal have different functions: strong binding site of MutS C-terminal contribute to association while weak binding site of MutS N-terminal regulate the relationship among Muts, mismatched DNA andβclamp. Our result suggest that (i) MutS scan the genome via binding toβclamp by its C-terminal strong binding site;(ii) MutS N-terminal stimulate the disassociation fromβclamp after MutS bind to s mismatch. This finding provide useful clues for better understanding the mechanisms of MutS scan for mismatch and start the mismatch repair pathway. In addition, we investigate binding activity to DNA mismatch of some proteins other than MutS, and the result implicated that there may exist supplementary pathways except for known MMR.