mismatch repair (MMR)

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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.

EXTERNAL DATABASES:
KEGG database - MMR - Homo sapiens (human) 
KEGG database - MMR - Mus musculus (mouse)
KEGG database - MMR - Caenorhabditis elegans (nematode)
KEGG database - MMR - Drosophila melanogaster (fruit fly)
KEGG database - MMR - Saccharomyces cerevisiae (budding yeast) 
KEGG database - MMR - DNA replication - Schizosaccharomyces pombe (fission yeast)
KEGG database - MMR - Escherichia coli K-12 MG1655
KEGG database - MMR - Arabidopsis thaliana (thale cress)


ABBREVIATIONS:
MMR


OTHER NAME(S):
DNA mismatch repair


RELATED DISEASES:


DAMAGES RECOGNIZED AND REMOVED:


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ORTHOLOGY CLASS Homo sapiens L. (human) [HSA] Mus musculus L. (mouse) [MMU] Caenorhabditis elegans Maupas (nematode) [CEL] Drosophila melanogaster Meigen (fruit fly) [DME] Saccharomyces cerevisiae Meyen ex E.C. Hansen (budding yeast) [SCE] Schizo-saccharomyces pombe Lindner (fission yeast) [SPO] Escherichia coli Migula (bacterium) K-12 MG1655 [ECO] Arabidopsis thaliana (L.) Heynh. (mouse-ear cress) [ATH]
ko:K10858 (DNA mismatch repair protein PMS2) PMS2 Pms2 pms-2 Pms2 PMS1 pms1 PMS1
ko:K10857 (exodeoxyribonuclease X [EC:3.1.11.-]) exoX
ko:K10756 (replication factor C subunit 3/5) RFC3
RFC5
Rfc5
Rfc3
rfc-3
ARPA
RfC3
RfC38
RFC3
RFC5
rfc3
rfc5
RFC3
putative RFC3/5
ko:K10755 (replication factor C subunit 2/4) RFC2
RFC4
Rfc4
Rfc2
rfc-4
rfc-2
RfC4
CG8142
RFC2
RFC4
rfc2
rfc4
RFC2/4
RFC2
ko:K10754 (replication factor C subunit 1) RFC1 Rfc1 rfc-1 Gnf1 RFC1 rfc1 AtRFC1
ko:K10747 (DNA ligase 1 [EC:6.5.1.1]) LIG1 Lig1 lig-1 DmDNA Lig I CDC9 adl1
cdc17
At1g49250
ATLIG1
ko:K10746 (exonuclease 1 [EC:3.1.-.-]) EXO1 (HEX1) Exo1 gi:17553464 tos EXO1 exo1 gi:145324070
ko:K10741 (replication factor A4) RPA4
ko:K10740 (replication factor A3) RPA3 Rpa3 Dmel_CG15220 ssb3 At4g18590
F3C22_30
ko:K10739 (replication factor A2) RPA2 Rpa2 rpa-2
rpa-4
RPA2 RFA2 ssb2 RPA2
RPA32B
ko:K08739 (DNA mismatch repair protein MLH3) MLH3 Mlh3 MLH3 MLH3
ko:K08737 (DNA mismatch repair protein MSH6) MSH6 Msh6 msh-6 Msh6 MSH6 msh6 MSH6
ko:K08736 (DNA mismatch repair protein MSH3) MSH3 Msh3 MSH3 msh3 MSH3
ko:K08735 (DNA mismatch repair protein MSH2) MSH2 Msh2 msh-2 spel1 MSH2 msh2 MSH2
ko:K08734 (DNA mismatch repair protein MLH1) MLH1 Mlh1 mlh-1 Mlh1 MLH1 mlh1 MLH1
ko:K07466 (replication factor A1) RPA1 Rpa1 rpa-1 RpA-70 RFA1 ssb1 RPA1A
ko:K07462 (single-stranded-DNA-specific exonuclease [EC:3.1.-.-]) RecJ
ko:K07456 (DNA mismatch repair protein MutS2) gi:15217840
ko:K06223 (DNA adenine methylase [EC:2.1.1.72]) Dam
ko:K04802 (proliferating cell nuclear antigen) PCNA Pcna pcn-1 Mus209 (Pcna)
Pcna2
POL30 pcn1 PCNA1
PCNA2
ko:K03657 (DNA helicase II / ATP-dependent DNA helicase PcrA [EC:3.6.4.12]) SRS2 srs2 UvrD
ko:K03602 (exodeoxyribonuclease VII small subunit [EC:3.1.11.6]) xseB
ko:K03601 (exodeoxyribonuclease VII large subunit [EC:3.1.11.6]) xseA
ko:K03573 (DNA mismatch repair protein MutH) MutH
ko:K03572 (DNA mismatch repair protein MutL) MutL
ko:K03555 (DNA mismatch repair protein MutS) MutS
ko:K03505 (DNA polymerase delta subunit 4) POLD4 Pold4 cdm1 POLD4
ko:K03504 (DNA polymerase delta subunit 3) POLD3 Pold3 PolD3 CG3975
Dmel_CG3975
POL32 cdc27 POLD3
ko:K03111 (single-strand DNA-binding protein) SSBP1 Ssbp1 mtSSB Ssb At3g18580
ko:K02345 (DNA polymerase III subunit theta [EC:2.7.7.7]) HolE
ko:K02344 (DNA polymerase III subunit psi [EC:2.7.7.7]) HolD
ko:K02343 (DNA polymerase III subunit gamma/tau [EC:2.7.7.7]) DnaX
ko:K02342 (DNA polymerase III subunit epsilon [EC:2.7.7.7]) DnaQ
ko:K02341 (DNA polymerase III subunit delta' [EC:2.7.7.7]) HolB
ko:K02340 (DNA polymerase III subunit delta [EC:2.7.7.7]) HolA
ko:K02339 (DNA polymerase III subunit chi [EC:2.7.7.7]) HolC
ko:K02338 (DNA polymerase III subunit beta [EC:2.7.7.7]) DnaN
ko:K02337 (DNA polymerase III subunit alpha [EC:2.7.7.7]) DnaE (PolC)
ko:K02328 (DNA polymerase delta subunit 2) POLD2 Pold2 DNA Pol delta sub 2 DNA pol delta small sub POL31 cdc1 POLD2
ko:K02327 (DNA polymerase delta subunit 1 [EC:2.7.7.7]) POLδ (POLD) mPolδ (mPolD) DNA Pol delta DNApol-delta POL3
POL3
cdc6 POLD1
ko:K01972 (DNA ligase (NAD+) [EC:6.5.1.2]) DNA ligase I
DNA ligase B
ko:K01141 (exodeoxyribonuclease I [EC:3.1.11.1]) sbcB

Last modification date: Oct. 11, 2011