KEGG   PATHWAY: sma03430
sma03430                    Pathway                                
Mismatch repair - Streptomyces avermitilis
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
sma03430  Mismatch repair

Other DBs
GO: 0006298
Streptomyces avermitilis [GN:sma]
SAVERM_3463  uvrD1; putative ATP-dependent DNA helicase [KO:K03657] [EC:]
SAVERM_3072  uvrD4; putative ATP-dependent DNA helicase [KO:K03657] [EC:]
SAVERM_3076  adnB; putative ATP-dependent DNA helicase [KO:K03657] [EC:]
SAVERM_3211  xseA; putative exoribonuclease large subunit [KO:K03601] [EC:]
SAVERM_3212  xseB; putative exoribonuclease small subunit [KO:K03602] [EC:]
SAVERM_4288  ssb1; putative single-stranded DNA-binding protein [KO:K03111]
SAVERM_5365  ssb2; putative single-strand DNA-binding protein [KO:K03111]
SAVERM_6143  dnaE1; putative DNA polymerase III alpha subunit [KO:K02337] [EC:]
SAVERM_4317  dnaN1; putative DNA polymerase III beta subunit [KO:K02338] [EC:]
SAVERM_3362  dnaN2; putative DNA polymerase III beta subunit [KO:K02338] [EC:]
SAVERM_4150  dnaZX; putative DNA polymerase III gamma and tau subunit [KO:K02343] [EC:]
SAVERM_5558  holA; putative DNA polymerase III delta subunit [KO:K02340] [EC:]
SAVERM_4623  holB; putative DNA polymerase III delta prime subunit [KO:K02341] [EC:]
SAVERM_6439  dnaQ1; putative DNA polymerase III epsilon subunit [KO:K02342] [EC:]
SAVERM_2147  dnaQ3; putative DNA polymerase III epsilon subunit [KO:K02342] [EC:]
SAVERM_2004  putative siderophore biosynthesis protein/iron transport protein [KO:K02339] [EC:]
SAVERM_2748  ligA; putative DNA ligase [KO:K01972] [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)
KO pathway

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