KEGG   PATHWAY: hsa03430Help
Entry
hsa03430                    Pathway                                

Name
Mismatch repair - Homo sapiens (human)
Description
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.
Class
Genetic Information Processing; Replication and repair
BRITE hierarchy
Pathway map
Mismatch repair
hsa03430

All organismsOrtholog table
Module
RPA complex [PATH:hsa03430]
RF-C complex [PATH:hsa03430]
BRCA1-associated genome surveillance complex (BASC) [PATH:hsa03430]
Disease
H00876  
Mismatch repair deficiency
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
6742  
SSBP1; single-stranded DNA binding protein 1, mitochondrial [KO:K03111]
5395  
PMS2; PMS2 postmeiotic segregation increased 2 (S. cerevisiae) [KO:K10858]
4292  
MLH1; mutL homolog 1 [KO:K08734]
2956  
MSH6; mutS homolog 6 [KO:K08737]
4436  
MSH2; mutS homolog 2 [KO:K08735]
4437  
MSH3; mutS homolog 3 [KO:K08736]
27030  
MLH3; mutL homolog 3 [KO:K08739]
5981  
RFC1; replication factor C (activator 1) 1, 145kDa [KO:K10754]
5984  
RFC4; replication factor C (activator 1) 4, 37kDa [KO:K10755]
5982  
RFC2; replication factor C (activator 1) 2, 40kDa [KO:K10755]
5985  
RFC5; replication factor C (activator 1) 5, 36.5kDa [KO:K10756]
5983  
RFC3; replication factor C (activator 1) 3, 38kDa [KO:K10756]
5111  
PCNA; proliferating cell nuclear antigen [KO:K04802]
9156  
EXO1; exonuclease 1 [KO:K10746] [EC:3.1.-.-]
6117  
RPA1; replication protein A1, 70kDa [KO:K07466]
6118  
RPA2; replication protein A2, 32kDa [KO:K10739]
6119  
RPA3; replication protein A3, 14kDa [KO:K10740]
29935  
RPA4; replication protein A4, 30kDa [KO:K10741]
5424  
POLD1; polymerase (DNA directed), delta 1, catalytic subunit [KO:K02327] [EC:2.7.7.7]
5425  
POLD2; polymerase (DNA directed), delta 2, accessory subunit [KO:K02328]
10714  
POLD3; polymerase (DNA-directed), delta 3, accessory subunit [KO:K03504]
57804  
POLD4; polymerase (DNA-directed), delta 4, accessory subunit [KO:K03505]
3978  
LIG1; ligase I, DNA, ATP-dependent [KO:K10747] [EC:6.5.1.1]
Reference
  Authors
Jiricny J.
  Title
The multifaceted mismatch-repair system.
  Journal
Nat Rev Mol Cell Biol 7:335-46 (2006)
Reference
  Authors
Li GM.
  Title
Mechanisms and functions of DNA mismatch repair.
  Journal
Cell Res 18:85-98 (2008)
Reference
  Authors
Marti TM, Kunz C, Fleck O.
  Title
DNA mismatch repair and mutation avoidance pathways.
  Journal
J Cell Physiol 191:28-41 (2002)
Reference
  Authors
Ikejima M, Shimada T.
  Title
[Molecular mechanism of mismatch repair] Japanese
  Journal
Tanpakushitsu Kakusan Koso 46:1124-9 (2001)
Reference
(Japanese )
  Authors
Hanaoka F.
  Title
[DNA Replication and Repair] (In Japanese)
  Journal
Yodosha (2004)
KO pathway
 

DBGET integrated database retrieval system