The mismatch repair system (MMR) recognizes and corrects mismatched or unpaired 
bases caused mainly by DNA polymerase, and contributes to the fidelity of DNA 
replication in living cells. In Escherichia coli, the MutHLS system is known to 
function in MMR, and homologues of MutS and MutL are widely conserved in almost 
all organisms. However, the MutH endonuclease has not been found in the majority 
of organisms. Such organisms, including Thermus thermophilus HB8, often possess 
the so-called MutS2 protein, which is highly homologous to MutS but contains an 
extra C-terminal stretch. To elucidate the function of MutS2, we overexpressed 
and purified T. thermophilus MutS2 (ttMutS2). ttMutS2 demonstrated the ability 
to bind double-stranded (ds) DNA, but, unlike ttMutS, ttMutS2 showed no 
specificity for mismatched duplexes. ttMutS2 ATPase activity was also detected 
and was stimulated by dsDNA. Our results also showed that ttMutS2 incises dsDNA. 
ttMutS2 incises not only oligo dsDNA but also plasmid DNA, suggesting that 
ttMutS2 possesses an endonuclease activity. At low concentrations, the incision 
activity was not retained, but was promoted by T. thermophilus MutL.