DNA mismatch repair (WP531)

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]
last edited

Authors

Thomas, AlexanderPico, MaintBot, MartijnVanIersel, Khanspers, Egonw, and Eweitz

Cited In

Organism

Homo sapiens

Communities

CPTAC

Annotations

Pathway Ontology: DNA repair pathway mismatch repair pathway

Participants

Label Type Compact Identifier
ATP Metabolite hmdb:HMDB0000538
POLE GeneProduct ensembl:ENSG00000177084
EXO1 GeneProduct ensembl:ENSG00000174371
POLD1 GeneProduct ensembl:ENSG00000062822
LIG1 GeneProduct ensembl:ENSG00000105486
POLD2 GeneProduct ensembl:ENSG00000106628
POLD3 GeneProduct ensembl:ENSG00000077514
POLD4 GeneProduct ensembl:ENSG00000175482
RFC1 GeneProduct ensembl:ENSG00000035928
MSH6 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
PCNA GeneProduct ensembl:ENSG00000132646
RFC2 GeneProduct ensembl:ENSG00000049541
RFC3 GeneProduct ensembl:ENSG00000133119
RFC4 GeneProduct ensembl:ENSG00000163918
RFC5 GeneProduct ensembl:ENSG00000111445
PMS2 GeneProduct ensembl:ENSG00000122512
MLH1 GeneProduct ensembl:ENSG00000076242
RPA1 GeneProduct ensembl:ENSG00000132383
RPA3 GeneProduct ensembl:ENSG00000106399
RPA2 GeneProduct ensembl:ENSG00000117748
MSH3 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
EXO1 GeneProduct ensembl:ENSG00000174371
RPA1 GeneProduct ensembl:ENSG00000132383
RPA3 GeneProduct ensembl:ENSG00000106399
RPA2 GeneProduct ensembl:ENSG00000117748
MSH6 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
MSH3 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
MSH6 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
MSH3 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
PMS2 GeneProduct ensembl:ENSG00000122512
MLH1 GeneProduct ensembl:ENSG00000076242
EXO1 GeneProduct ensembl:ENSG00000174371
PCNA GeneProduct ensembl:ENSG00000132646
RPA1 GeneProduct ensembl:ENSG00000132383
RPA3 GeneProduct ensembl:ENSG00000106399
RPA2 GeneProduct ensembl:ENSG00000117748
POLE2 GeneProduct ensembl:ENSG00000100479
POLE3 GeneProduct ensembl:ENSG00000148229
POLE4 GeneProduct ensembl:ENSG00000115350
RPA1 GeneProduct ensembl:ENSG00000132383
RPA3 GeneProduct ensembl:ENSG00000106399
RPA2 GeneProduct ensembl:ENSG00000117748
MSH6 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
MSH3 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
PCNA GeneProduct ensembl:ENSG00000132646
ATP Metabolite hmdb:HMDB0000538
PMS2 GeneProduct ensembl:ENSG00000122512
MLH1 GeneProduct ensembl:ENSG00000076242
POLE GeneProduct ensembl:ENSG00000177084
POLD1 GeneProduct ensembl:ENSG00000062822
POLD2 GeneProduct ensembl:ENSG00000106628
POLD3 GeneProduct ensembl:ENSG00000077514
POLD4 GeneProduct ensembl:ENSG00000175482
POLE2 GeneProduct ensembl:ENSG00000100479
POLE3 GeneProduct ensembl:ENSG00000148229
POLE4 GeneProduct ensembl:ENSG00000115350
PCNA GeneProduct ensembl:ENSG00000132646
MSH6 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
MSH3 GeneProduct ensembl:ENSG00000116062
MSH2 GeneProduct ensembl:ENSG00000095002
PMS2 GeneProduct ensembl:ENSG00000122512
MLH1 GeneProduct ensembl:ENSG00000076242
RPA1 GeneProduct ensembl:ENSG00000132383
RPA3 GeneProduct ensembl:ENSG00000106399
RPA2 GeneProduct ensembl:ENSG00000117748
RPA1 GeneProduct ensembl:ENSG00000132383
RPA3 GeneProduct ensembl:ENSG00000106399
RPA2 GeneProduct ensembl:ENSG00000117748
RPA1 GeneProduct ensembl:ENSG00000132383
RPA3 GeneProduct ensembl:ENSG00000106399
RPA2 GeneProduct ensembl:ENSG00000117748
PCNA GeneProduct ensembl:ENSG00000132646
LIG1 GeneProduct ensembl:ENSG00000105486
POLE GeneProduct ensembl:ENSG00000177084
POLE2 GeneProduct ensembl:ENSG00000100479
POLE3 GeneProduct ensembl:ENSG00000148229
POLE4 GeneProduct ensembl:ENSG00000115350
POLD1 GeneProduct ensembl:ENSG00000062822
POLD2 GeneProduct ensembl:ENSG00000106628
POLD3 GeneProduct ensembl:ENSG00000077514
POLD4 GeneProduct ensembl:ENSG00000175482
LIG1 GeneProduct ensembl:ENSG00000105486
LIG1 GeneProduct ensembl:ENSG00000105486
POLE GeneProduct ensembl:ENSG00000177084
POLE2 GeneProduct ensembl:ENSG00000100479
POLE3 GeneProduct ensembl:ENSG00000148229
POLE4 GeneProduct ensembl:ENSG00000115350
POLD1 GeneProduct ensembl:ENSG00000062822
POLD2 GeneProduct ensembl:ENSG00000106628
POLD3 GeneProduct ensembl:ENSG00000077514
POLD4 GeneProduct ensembl:ENSG00000175482

References

  1. Iyer RR, Pluciennik A, Burdett V, Modrich PL. DNA mismatch repair: functions and mechanisms. Chem Rev. 2006 Feb;106(2):302–23. PubMed Europe PMC Scholia
  2. Hsieh P, Zhang Y. The Devil is in the details for DNA mismatch repair. Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):3552–4. PubMed Europe PMC Scholia