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afr03430                    Pathway                                

Mismatch repair - Acidithiobacillus ferrooxidans ATCC 23270
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
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Mismatch repair

All organismsOrtholog table
DNA polymerase III complex, bacteria [PATH:afr03430]
Other DBs
Acidithiobacillus ferrooxidans ATCC 23270 [GN:afr]
mutS; DNA mismatch repair protein MutS [KO:K03555]
MutS2 family protein [KO:K07456]
MutS domain V protein [KO:K07456]
mutL; mismatch repair protein MutL [KO:K03572]
uvrD; DNA helicase II [KO:K03657] [EC:]
xseA; exodeoxyribonuclease VII, large subunit [KO:K03601] [EC:]
xseB; exodeoxyribonuclease VII, small subunit [KO:K03602] [EC:]
exodeoxyribonuclease X, putative [KO:K10857] [EC:3.1.11.-]
recJ; single-stranded-DNA-specific exonuclease RecJ [KO:K07462] [EC:3.1.-.-]
ssb-2; single-strand binding protein [KO:K03111]
ssb-1; single-strand binding protein [KO:K03111]
ssb-3; single-strand binding protein [KO:K03111]
dnaE; DNA polymerase III, alpha subunit [KO:K02337] [EC:]
dnaN; DNA polymerase III, beta subunit [KO:K02338] [EC:]
dnaX; DNA polymerase III, subunits gamma and tau [KO:K02343] [EC:]
holA; DNA polymerase III, delta subunit [KO:K02340] [EC:]
holB; DNA polymerase III, delta prime subunit [KO:K02341] [EC:]
dnaQ; DNA polymerase III, epsilon subunit [KO:K02342] [EC:]
holC; DNA polymerase III, chi subunit [KO:K02339] [EC:]
ligA; DNA ligase, NAD-dependent [KO:K01972] [EC:]
DNA ligase, NAD-dependent, putative [KO:K01972] [EC:]
methyltransferase, putative [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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