KEGG   PATHWAY: oas03430
Entry
oas03430                    Pathway                                

Name
Mismatch repair - Ovis aries (sheep)
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
oas03430  Mismatch repair
oas03430

Other DBs
GO: 0006298
Organism
Ovis aries (sheep) [GN:oas]
Gene
101108908  SSBP1; single-stranded DNA-binding protein, mitochondrial [KO:K03111]
101115595  PMS2; mismatch repair endonuclease PMS2 isoform X4 [KO:K10858]
101108344  MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:K08734]
101107426  MSH6; DNA mismatch repair protein Msh6 [KO:K08737]
101107944  MSH2; DNA mismatch repair protein Msh2 [KO:K08735]
101121679  MSH3; DNA mismatch repair protein Msh3 [KO:K08736]
101109183  MLH3; DNA mismatch repair protein Mlh3 isoform X1 [KO:K08739]
101109450  RFC1; replication factor C subunit 1 isoform X1 [KO:K10754]
101110382  RFC2; replication factor C subunit 2 isoform X1 [KO:K10755]
101112103  RFC4; replication factor C subunit 4 [KO:K10755]
101108399  RFC3; replication factor C subunit 3 [KO:K10756]
101109740  RFC5; replication factor C subunit 5 isoform X1 [KO:K10756]
443155  PCNA; proliferating cell nuclear antigen [KO:K04802]
101120258  EXO1; exonuclease 1 [KO:K10746] [EC:3.1.-.-]
100302100  RPA1; replication protein A 70 kDa DNA-binding subunit [KO:K07466]
101105309  RPA2; replication protein A 32 kDa subunit [KO:K10739]
101121087  RPA3; replication protein A 14 kDa subunit [KO:K10740]
105605654  RPA4; LOW QUALITY PROTEIN: replication protein A 30 kDa subunit [KO:K10741]
101117012  POLD1; DNA polymerase delta catalytic subunit [KO:K02327] [EC:2.7.7.7]
101117838  POLD2; DNA polymerase delta subunit 2 isoform X1 [KO:K02328]
101106622  POLD3; DNA polymerase delta subunit 3 [KO:K03504]
101118743  POLD4; DNA polymerase delta subunit 4 [KO:K03505]
101104173  LIG1; DNA ligase 1 isoform X1 [KO:K10747] [EC:6.5.1.1 6.5.1.6 6.5.1.7]
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)
Related
pathway
oas05210  Colorectal cancer
KO pathway
ko03430   
LinkDB

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