KEGG PATHWAY: ko03430

PATHWAY: ko03430

Entry

ko03430 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

ko03430

Mismatch repair

Module

M00260	DNA polymerase III complex, bacteria [PATH:ko03430]
M00288	RPA complex [PATH:ko03430]
M00289	RF-C complex [PATH:ko03430]
M00295	BRCA1-associated genome surveillance complex (BASC) [PATH:ko03430]

Disease

H00876

Mismatch repair deficiency

Other DBs

BSID:

453

GO:

0006298

Orthology

K03555	DNA mismatch repair protein MutS
K07456	DNA mismatch repair protein MutS2
K03572	DNA mismatch repair protein MutL
K03573	DNA mismatch repair protein MutH
K03657	DNA helicase II / ATP-dependent DNA helicase PcrA [EC:3.6.4.12]
K01141	exodeoxyribonuclease I [EC:3.1.11.1]
K03601	exodeoxyribonuclease VII large subunit [EC:3.1.11.6]
K03602	exodeoxyribonuclease VII small subunit [EC:3.1.11.6]
K10857	exodeoxyribonuclease X [EC:3.1.11.-]
K07462	single-stranded-DNA-specific exonuclease [EC:3.1.-.-]
K03111	single-strand DNA-binding protein
K02337	DNA polymerase III subunit alpha [EC:2.7.7.7]
K03763	DNA polymerase III subunit alpha, Gram-positive type [EC:2.7.7.7]
K02338	DNA polymerase III subunit beta [EC:2.7.7.7]
K02343	DNA polymerase III subunit gamma/tau [EC:2.7.7.7]
K02340	DNA polymerase III subunit delta [EC:2.7.7.7]
K02341	DNA polymerase III subunit delta' [EC:2.7.7.7]
K02342	DNA polymerase III subunit epsilon [EC:2.7.7.7]
K14159	ribonuclease HI / DNA polymerase III subunit epsilon [EC:2.7.7.7 3.1.26.4]
K02345	DNA polymerase III subunit theta [EC:2.7.7.7]
K02339	DNA polymerase III subunit chi [EC:2.7.7.7]
K02344	DNA polymerase III subunit psi [EC:2.7.7.7]
K01971	DNA ligase (ATP) [EC:6.5.1.1]
K01972	DNA ligase (NAD+) [EC:6.5.1.2]
K06223	DNA adenine methylase [EC:2.1.1.72]
K10858	DNA mismatch repair protein PMS2
K08734	DNA mismatch repair protein MLH1
K08737	DNA mismatch repair protein MSH6
K08735	DNA mismatch repair protein MSH2
K08736	DNA mismatch repair protein MSH3
K08739	DNA mismatch repair protein MLH3
K10754	replication factor C subunit 1
K10755	replication factor C subunit 2/4
K10756	replication factor C subunit 3/5
K04802	proliferating cell nuclear antigen
K10746	exonuclease 1 [EC:3.1.-.-]
K07466	replication factor A1
K10739	replication factor A2
K10740	replication factor A3
K10741	replication factor A4
K02327	DNA polymerase delta subunit 1 [EC:2.7.7.7]
K02328	DNA polymerase delta subunit 2
K03504	DNA polymerase delta subunit 3
K03505	DNA polymerase delta subunit 4
K10747	DNA ligase 1 [EC:6.5.1.1]

Reference

PMID:16612326

Authors

Jiricny J.

Title

The multifaceted mismatch-repair system.

Journal

Nat Rev Mol Cell Biol 7:335-46 (2006)

Reference

PMID:18157157

Authors

Li GM.

Title

Mechanisms and functions of DNA mismatch repair.

Journal

Cell Res 18:85-98 (2008)

Reference

PMID:11920679

Authors

Marti TM, Kunz C, Fleck O.

Title

DNA mismatch repair and mutation avoidance pathways.

Journal

J Cell Physiol 191:28-41 (2002)

Reference

PMID:11436301

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)

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Ontology (2)   
   KEGG BRITE (1)   
   GO (1)   
Pathway (7)   
   KEGG PATHWAY (2)   
   KEGG MODULE (4)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Chemical reaction (10)   
   KEGG ENZYME (10)   
Gene (45)   
   KEGG ORTHOLOGY (45)   
Literature (4)   
   PubMed (4)   
All databases (69)   

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