MutH

MutH is a DNA mismatch repair endonuclease found in many bacteria, including Escherichia coli. It is encoded by the mutH gene and is a component of the MutHLS repair system, which also includes MutS and MutL. This system corrects mispaired bases and small insertion-deletion loops introduced during DNA replication.

MutH's key role is strand discrimination. After replication, the newly synthesized strand is temporarily unmethylated at GATC sequences by Dam methylase, while the parental strand is methylated. MutS recognizes a base-pair mismatch and recruits MutL. The MutS–MutL complex activates MutH, which cleaves the unmethylated strand at a nearby GATC site, creating a nick in the strand containing the error.

Following nicking, exonucleases remove the segment of DNA containing the mismatch from the nick to beyond the error. DNA polymerase III then resynthesizes the gap, and DNA ligase seals the final nick. This process restores the correct sequence and preserves genome integrity.

MutH typically functions as a Mg2+-dependent endonuclease and interacts with MutL as part of a coordinated repair complex. MutH activity is lost in mutH mutants, which exhibit a mutator phenotype due to failure to repair mismatches efficiently. Some bacteria lack MutH and rely on alternative strand discrimination pathways; in eukaryotes, the MutS/MutL homologs (MSH/MLH) carry out a parallel function, though without a MutH-like endonuclease.