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 [https://pubmed.ncbi.nlm.nih.gov/28356513/ Hsieh et al], with additional information from [http://repairtoire.genesilico.pl/Pathway/10/ REPAIRtoire], [https://en.wikipedia.org/wiki/DNA_mismatch_repair Wikipedia] and [https://www.genome.jp/dbget-bin/www_bget?pathway+hsa03430 KEGG]. The description was adapted from REPAIRtoire, layout is based on KEGG. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP531 CPTAC Assay Portal] b06 a42 DNA repair pathway PW:0000099 Pathway Ontology mismatch repair pathway PW:0000662 Pathway Ontology 16464007 PubMed DNA mismatch repair: functions and mechanisms. Chem Rev 2006 Iyer RR Pluciennik A Burdett V Modrich PL 28356513 PubMed The Devil is in the details for DNA mismatch repair. Proc Natl Acad Sci U S A 2017 Hsieh P Zhang Y