KEGG   PATHWAY: eco03430
eco03430                    Pathway                                

Mismatch repair - Escherichia coli K-12 MG1655
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
eco03430  Mismatch repair

Other DBs
GO: 0006298
Escherichia coli K-12 MG1655 [GN:eco]
b2733  mutS; DNA mismatch repair protein MutS [KO:K03555]
b4170  mutL; DNA mismatch repair protein MutL [KO:K03572]
b2831  mutH; DNA mismatch repair protein MutH [KO:K03573]
b3813  uvrD; ssDNA translocase and dsDNA helicase - DNA helicase II [KO:K03657] [EC:]
b2011  sbcB; exodeoxyribonuclease I [KO:K01141] [EC:]
b2509  xseA; exodeoxyribonuclease VII subunit XseA [KO:K03601] [EC:]
b0422  xseB; exodeoxyribonuclease VII subunit XseB [KO:K03602] [EC:]
b1844  exoX; exonuclease X [KO:K10857] [EC:3.1.11.-]
b2892  recJ; ssDNA-specific exonuclease RecJ [KO:K07462] [EC:3.1.-.-]
b4059  ssb; ssDNA-binding protein [KO:K03111]
b0184  dnaE; DNA polymerase III subunit alpha [KO:K02337] [EC:]
b3701  dnaN; beta sliding clamp [KO:K02338] [EC:]
b0470  dnaX; DNA polymerase III subunit tau [KO:K02343] [EC:]
b0640  holA; DNA polymerase III subunit delta [KO:K02340] [EC:]
b1099  holB; DNA polymerase III subunit delta' [KO:K02341] [EC:]
b0215  dnaQ; DNA polymerase III subunit epsilon [KO:K02342] [EC:]
b1842  holE; DNA polymerase III subunit theta [KO:K02345] [EC:]
b4259  holC; DNA polymerase III subunit chi [KO:K02339] [EC:]
b4372  holD; DNA polymerase III subunit psi [KO:K02344] [EC:]
b2411  ligA; DNA ligase [KO:K01972] [EC:]
b3647  ligB; DNA ligase B [KO:K01972] [EC:]
b3387  dam; DNA adenine methyltransferase [KO:K06223] [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] Japanese
Tanpakushitsu Kakusan Koso 46:1124-9 (2001)
KO pathway

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