ENTRY ko03430 Pathway NAME Mismatch repair DESCRIPTION DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR corrects DNA mismatches generated during DNA replication, thereby preventing mutations from becoming permanent in dividing cells. MMR also suppresses homologous recombination and was recently shown to play a role in DNA damage signaling. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including HNPCC, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems. The Escherichia coli MMR pathway has been extensively studied and is well characterized. In E. coli, the mismatch-activated MutS-MutL-ATP complex licenses MutH to incise the nearest unmethylated GATC sequence. UvrD and an exonuclease generate a gap. This gap is filled by pol III and DNA ligase. The GATC sites are then methylated by Dam. Several human MMR proteins have been identified based on their homology to E. coli MMR proteins. These include human homologs of MutS and MutL. Although E. coli MutS and MutL proteins are homodimers, human MutS and MutL homologs are heterodimers. The role of hemimethylated dGATC sites as a signal for strand discrimination is not conserved from E. coli to human. Human MMR is presumed to be nick-directed in vivo, and is thought to discriminate daughter and template strands using a strand-specific nick. CLASS Genetic Information Processing; Replication and repair PATHWAY_MAP ko03430 Mismatch repair DBLINKS GO: 0006298 ORTHOLOGY K03555 DNA mismatch repair protein MutS K07456 DNA mismatch repair protein MutS2 K03572 DNA mismatch repair protein MutL K03573 DNA mismatch repair protein MutH K03657 ATP-dependent DNA helicase UvrD/PcrA [EC:5.6.2.4] K01141 exodeoxyribonuclease I [EC:3.1.11.1] K03601 exodeoxyribonuclease VII large subunit [EC:3.1.11.6] K03602 exodeoxyribonuclease VII small subunit [EC:3.1.11.6] K10857 exodeoxyribonuclease X [EC:3.1.11.-] K07462 single-stranded-DNA-specific exonuclease [EC:3.1.-.-] K03111 single-strand DNA-binding protein K02337 DNA polymerase III subunit alpha [EC:2.7.7.7] K03763 DNA polymerase III subunit alpha, Gram-positive type [EC:2.7.7.7] K02338 DNA polymerase III subunit beta [EC:2.7.7.7] K02343 DNA polymerase III subunit gamma/tau [EC:2.7.7.7] K02340 DNA polymerase III subunit delta [EC:2.7.7.7] K02341 DNA polymerase III subunit delta' [EC:2.7.7.7] K02342 DNA polymerase III subunit epsilon [EC:2.7.7.7] K14159 ribonuclease HI / DNA polymerase III subunit epsilon [EC:3.1.26.4 2.7.7.7] K02345 DNA polymerase III subunit theta [EC:2.7.7.7] K02339 DNA polymerase III subunit chi [EC:2.7.7.7] K02344 DNA polymerase III subunit psi [EC:2.7.7.7] K01972 DNA ligase (NAD+) [EC:6.5.1.2] K06223 DNA adenine methylase [EC:2.1.1.72] K10858 DNA mismatch repair protein PMS2 K08734 DNA mismatch repair protein MLH1 K08737 DNA mismatch repair protein MSH6 K08735 DNA mismatch repair protein MSH2 K08736 DNA mismatch repair protein MSH3 K08739 DNA mismatch repair protein MLH3 K10754 replication factor C subunit 1 K10755 replication factor C subunit 2/4 K10756 replication factor C subunit 3/5 K04802 proliferating cell nuclear antigen K10746 exonuclease 1 [EC:3.1.-.-] K07466 replication factor A1 K10739 replication factor A2 K10740 replication factor A3 K10741 replication factor A4 K02327 DNA polymerase delta subunit 1 [EC:2.7.7.7] K02328 DNA polymerase delta subunit 2 K03504 DNA polymerase delta subunit 3 K03505 DNA polymerase delta subunit 4 K10747 DNA ligase 1 [EC:6.5.1.1 6.5.1.6 6.5.1.7] REFERENCE PMID:16612326 AUTHORS Jiricny J. TITLE The multifaceted mismatch-repair system. JOURNAL Nat Rev Mol Cell Biol 7:335-46 (2006) DOI:10.1038/nrm1907 REFERENCE PMID:18157157 AUTHORS Li GM. TITLE Mechanisms and functions of DNA mismatch repair. JOURNAL Cell Res 18:85-98 (2008) DOI:10.1038/cr.2007.115 REFERENCE PMID:11920679 AUTHORS Marti TM, Kunz C, Fleck O. TITLE DNA mismatch repair and mutation avoidance pathways. JOURNAL J Cell Physiol 191:28-41 (2002) DOI:10.1002/jcp.10077 REFERENCE PMID:11436301 AUTHORS Ikejima M, Shimada T. TITLE [Molecular mechanism of mismatch repair] JOURNAL Tanpakushitsu Kakusan Koso 46:1124-9 (2001) REL_PATHWAY ko05210 Colorectal cancer ///