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
hsa03430  Mismatch repair
hsa03430

Ortholog table
Module
hsa_M00288  RPA complex [PATH:hsa03430]
hsa_M00289  RF-C complex [PATH:hsa03430]
hsa_M00295  BRCA1-associated genome surveillance complex (BASC) [PATH:hsa03430]
Disease
H00876  Mismatch repair deficiency
Other DBs
BSID: 83045
GO: 0006298
Organism
Homo sapiens (human) [GN:hsa]
Gene
6742  SSBP1; single stranded DNA binding protein 1 [KO:K03111]
5395  PMS2; PMS1 homolog 2, mismatch repair system component [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 subunit 1 [KO:K10754]
5984  RFC4; replication factor C subunit 4 [KO:K10755]
5982  RFC2; replication factor C subunit 2 [KO:K10755]
5985  RFC5; replication factor C subunit 5 [KO:K10756]
5983  RFC3; replication factor C subunit 3 [KO:K10756]
5111  PCNA; proliferating cell nuclear antigen [KO:K04802]
9156  EXO1; exonuclease 1 [KO:K10746] [EC:3.1.-.-]
6117  RPA1; replication protein A1 [KO:K07466]
6118  RPA2; replication protein A2 [KO:K10739]
6119  RPA3; replication protein A3 [KO:K10740]
29935  RPA4; replication protein A4 [KO:K10741]
5424  POLD1; DNA polymerase delta 1, catalytic subunit [KO:K02327] [EC:2.7.7.7]
5425  POLD2; DNA polymerase delta 2, accessory subunit [KO:K02328]
10714  POLD3; DNA polymerase delta 3, accessory subunit [KO:K03504]
57804  POLD4; DNA polymerase delta 4, accessory subunit [KO:K03505]
3978  LIG1; DNA ligase 1 [KO:K10747] [EC:6.5.1.7 6.5.1.6 6.5.1.1]
Reference
  Authors
Jiricny J.
  Title
The multifaceted mismatch-repair system.
  Journal
Nat Rev Mol Cell Biol 7:335-46 (2006)
DOI:10.1038/nrm1907
Reference
  Authors
Li GM.
  Title
Mechanisms and functions of DNA mismatch repair.
  Journal
Cell Res 18:85-98 (2008)
DOI:10.1038/cr.2007.115
Reference
  Authors
Marti TM, Kunz C, Fleck O.
  Title
DNA mismatch repair and mutation avoidance pathways.
  Journal
J Cell Physiol 191:28-41 (2002)
DOI:10.1002/jcp.10077
Reference
  Authors
Ikejima M, Shimada T.
  Title
[Molecular mechanism of mismatch repair] Japanese
  Journal
Tanpakushitsu Kakusan Koso 46:1124-9 (2001)
KO pathway
ko03430   

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