Mismatch repair - Ovis aries (sheep)
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.
Genetic Information Processing; Replication and repair
Ovis aries (sheep) [GN:
SSBP1; single-stranded DNA-binding protein, mitochondrial [KO:
PMS2; mismatch repair endonuclease PMS2 isoform X4 [KO:
MLH1; DNA mismatch repair protein Mlh1 isoform X1 [KO:
MSH6; DNA mismatch repair protein Msh6 [KO:
MSH2; DNA mismatch repair protein Msh2 [KO:
MSH3; DNA mismatch repair protein Msh3 [KO:
MLH3; DNA mismatch repair protein Mlh3 isoform X1 [KO:
RFC1; replication factor C subunit 1 isoform X1 [KO:
RFC2; replication factor C subunit 2 isoform X1 [KO:
RFC4; replication factor C subunit 4 [KO:
RFC3; replication factor C subunit 3 [KO:
RFC5; replication factor C subunit 5 isoform X1 [KO:
PCNA; proliferating cell nuclear antigen [KO:
EXO1; exonuclease 1 [KO:
RPA1; replication protein A 70 kDa DNA-binding subunit [KO:
RPA2; replication protein A 32 kDa subunit [KO:
RPA3; replication protein A 14 kDa subunit [KO:
RPA4; LOW QUALITY PROTEIN: replication protein A 30 kDa subunit [KO:
POLD1; DNA polymerase delta catalytic subunit [KO:
POLD2; DNA polymerase delta subunit 2 isoform X1 [KO:
POLD3; DNA polymerase delta subunit 3 [KO:
POLD4; DNA polymerase delta subunit 4 [KO:
LIG1; DNA ligase 1 isoform X1 [KO:
The multifaceted mismatch-repair system.
Nat Rev Mol Cell Biol 7:335-46 (2006)
Mechanisms and functions of DNA mismatch repair.
Cell Res 18:85-98 (2008)
Marti TM, Kunz C, Fleck O.
DNA mismatch repair and mutation avoidance pathways.
J Cell Physiol 191:28-41 (2002)
Ikejima M, Shimada T.
[Molecular mechanism of mismatch repair] Japanese
Tanpakushitsu Kakusan Koso 46:1124-9 (2001)
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