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 K01141 sbcB, exoI; exodeoxyribonuclease I [EC:3.1.11.1] K01972 E6.5.1.2, ligA, ligB; DNA ligase (NAD+) [EC:6.5.1.2] K02327 POLD1; DNA polymerase delta subunit 1 [EC:2.7.7.7] K02328 POLD2; DNA polymerase delta subunit 2 K02337 dnaE; DNA polymerase III subunit alpha [EC:2.7.7.7] K02338 dnaN; DNA polymerase III subunit beta [EC:2.7.7.7] K02339 holC; DNA polymerase III subunit chi [EC:2.7.7.7] K02340 holA; DNA polymerase III subunit delta [EC:2.7.7.7] K02341 holB; DNA polymerase III subunit delta' [EC:2.7.7.7] K02342 dnaQ; DNA polymerase III subunit epsilon [EC:2.7.7.7] K02343 dnaX; DNA polymerase III subunit gamma/tau [EC:2.7.7.7] K02344 holD; DNA polymerase III subunit psi [EC:2.7.7.7] K02345 holE; DNA polymerase III subunit theta [EC:2.7.7.7] K03111 ssb; single-strand DNA-binding protein K03504 POLD3; DNA polymerase delta subunit 3 K03505 POLD4; DNA polymerase delta subunit 4 K03555 mutS; DNA mismatch repair protein MutS K03572 mutL; DNA mismatch repair protein MutL K03573 mutH; DNA mismatch repair protein MutH K03601 xseA; exodeoxyribonuclease VII large subunit [EC:3.1.11.6] K03602 xseB; exodeoxyribonuclease VII small subunit [EC:3.1.11.6] K03657 uvrD, pcrA; ATP-dependent DNA helicase UvrD/PcrA [EC:5.6.2.4] K03763 polC; DNA polymerase III subunit alpha, Gram-positive type [EC:2.7.7.7] K04802 PCNA; proliferating cell nuclear antigen K06223 dam; DNA adenine methylase [EC:2.1.1.72] K07456 mutS2; DNA mismatch repair protein MutS2 K07462 recJ; single-stranded-DNA-specific exonuclease [EC:3.1.-.-] K07466 RFA1, RPA1, rpa; replication factor A1 K08734 MLH1; DNA mismatch repair protein MLH1 K08735 MSH2; DNA mismatch repair protein MSH2 K08736 MSH3; DNA mismatch repair protein MSH3 K08737 MSH6; DNA mismatch repair protein MSH6 K08739 MLH3; DNA mismatch repair protein MLH3 K10739 RFA2, RPA2; replication factor A2 K10740 RPA3; replication factor A3 K10741 RPA4; replication factor A4 K10746 EXO1; exonuclease 1 [EC:3.1.-.-] K10747 LIG1; DNA ligase 1 [EC:6.5.1.1 6.5.1.6 6.5.1.7] K10754 RFC1; replication factor C subunit 1 K10755 RFC2_4; replication factor C subunit 2/4 K10756 RFC3_5; replication factor C subunit 3/5 K10857 exoX; exodeoxyribonuclease X [EC:3.1.11.-] K10858 PMS2; DNA mismatch repair protein PMS2 K14159 rnhA-dnaQ; ribonuclease HI / DNA polymerase III subunit epsilon [EC:3.1.26.4 2.7.7.7] 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 ///