KEGG   PATHWAY: map03430
Entry
map03430                    Pathway                                
Name
Mismatch repair
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
Pathway map
map03430  Mismatch repair
map03430

Other DBs
GO: 0006298
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]
  Journal
Tanpakushitsu Kakusan Koso 46:1124-9 (2001)
Related
pathway
map05210  Colorectal cancer
KO pathway
ko03430   
LinkDB

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