DNA mismatch repair (Homo sapiens)

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DNA mismatch repair (MMR) is responsible for correcting mismatches and small insertions and deletions caused during replication and recombination. In eukaryotes the process of MMR is initiated by MutSalpha and MutLalpha, homologs of the E.coli proteins MutS and MutL. MutS homologs first recognize the error in DNA, and then physically interact with MutL, which activates other proteins that remove the erroneous DNA strand and synthesize a new one.

In vitro MMR requires a nick requires a preexisting nick (single-strand gap) in the DNA substrate. Similarly, it is thought that for in vivo MMR in eukaryotes, newly synthesized lagging-strand DNA transiently contains nicks (before being sealed by DNA ligase) which provides a signal that directs mismatch proofreading systems to the appropriate strandThis pathway describes the slightly different mechanisms for MMR based on the location of the nick in relation to the mismatch (5' and 3').

Mutations in the genes coding human MutS and MutL homologs have been linked with the Lynch syndrome, which is characterized by an increased risk of developing cancer.

This pathway is based on figure 1 from Hsieh et al, with additional information from REPAIRtoire, Wikipedia and KEGG. The description was adapted from REPAIRtoire, layout is based on KEGG.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal