KEGG   PATHWAY: ko03430
ko03430                     Pathway                                
Mismatch repair
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.
Genetic Information Processing; Replication and repair
Pathway map
ko03430  Mismatch repair

Other DBs
GO: 0006298
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:]
K01141  exodeoxyribonuclease I [EC:]
K03601  exodeoxyribonuclease VII large subunit [EC:]
K03602  exodeoxyribonuclease VII small subunit [EC:]
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:]
K03763  DNA polymerase III subunit alpha, Gram-positive type [EC:]
K02338  DNA polymerase III subunit beta [EC:]
K02343  DNA polymerase III subunit gamma/tau [EC:]
K02340  DNA polymerase III subunit delta [EC:]
K02341  DNA polymerase III subunit delta' [EC:]
K02342  DNA polymerase III subunit epsilon [EC:]
K14159  ribonuclease HI / DNA polymerase III subunit epsilon [EC:]
K02345  DNA polymerase III subunit theta [EC:]
K02339  DNA polymerase III subunit chi [EC:]
K02344  DNA polymerase III subunit psi [EC:]
K01972  DNA ligase (NAD+) [EC:]
K06223  DNA adenine methylase [EC:]
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:]
K02328  DNA polymerase delta subunit 2
K03504  DNA polymerase delta subunit 3
K03505  DNA polymerase delta subunit 4
K10747  DNA ligase 1 [EC:]
Jiricny J.
The multifaceted mismatch-repair system.
Nat Rev Mol Cell Biol 7:335-46 (2006)
Li GM.
Mechanisms and functions of DNA mismatch repair.
Cell Res 18:85-98 (2008)
Marti TM, Kunz C, Fleck O.
DNA mismatch repair and mutation avoidance pathways.
J Cell Physiol 191:28-41 (2002)
Ikejima M, Shimada T.
[Molecular mechanism of mismatch repair]
Tanpakushitsu Kakusan Koso 46:1124-9 (2001)
ko05210  Colorectal cancer

DBGET integrated database retrieval system