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ipa03430                    Pathway                                

Mismatch repair - Isosphaera pallida
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.
09120 Genetic Information Processing; 09124 Replication and repair
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ipa03430  Mismatch repair

Ortholog table
Other DBs
BSID: 197493
GO: 0006298
Isosphaera pallida [GN:ipa]
Isop_0373  DNA mismatch repair protein MutS [KO:K03555]
Isop_3309  DNA mismatch repair protein MutS domain protein [KO:K07456]
Isop_1688  DNA mismatch repair protein MutL [KO:K03572]
Isop_2011  UvrD/REP helicase [KO:K03657] [EC:]
Isop_2865  UvrD/REP helicase [KO:K03657] [EC:]
Isop_0187  exodeoxyribonuclease VII, large subunit [KO:K03601] [EC:]
Isop_1786  exodeoxyribonuclease VII, small subunit [KO:K03602] [EC:]
Isop_2353  single-stranded-DNA-specific exonuclease RecJ [KO:K07462] [EC:3.1.-.-]
Isop_2890  single-strand binding protein [KO:K03111]
Isop_1325  DNA polymerase III, alpha subunit [KO:K02337] [EC:]
Isop_2145  DNA polymerase III, beta subunit [KO:K02338] [EC:]
Isop_2992  DNA polymerase III, subunits gamma and tau [KO:K02343] [EC:]
Isop_1265  DNA polymerase III, delta subunit [KO:K02340] [EC:]
Isop_0907  DNA polymerase III, delta prime subunit [KO:K02341] [EC:]
Isop_1161  DNA ligase, NAD-dependent [KO:K01972] [EC:]
Isop_3557  D12 class N6 adenine-specific DNA methyltransferase [KO:K06223] [EC:]
Isop_2715  ATP dependent DNA ligase [KO:K10747] [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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