D
IPR000432

DNA mismatch repair protein MutS, C-terminal

InterPro entry
Short nameDNA_mismatch_repair_MutS_C
Overlapping
homologous
superfamilies
 
domain relationships

Description

Mismatch repair contributes to the overall fidelity of DNA replication and is essential for combating the adverse effects of damage to the genome. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. The post-replicative Mismatch Repair System (MMRS) of Escherichia coli involves MutS (Mutator S), MutL and MutH proteins, and acts to correct point mutations or small insertion/deletion loops produced during DNA replication
[2]
. MutS and MutL are involved in preventing recombination between partially homologous DNA sequences. The assembly of MMRS is initiated by MutS, which recognises and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base
[3]
. MutS can also collaborate with methyltransferases in the repair of O(6)-methylguanine damage, which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch
[4]
. MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level
[5]
. Only one monomer recognises the mismatch specifically and has ADP bound. Non-specific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. Mismatch binding induces ATP uptake and a conformational change in the MutS protein, resulting in a clamp that translocates on DNA.

This entry represents the C-terminal domain found in proteins in the MutS family of DNA mismatch repair proteins. The C-terminal region of MutS is comprised of the ATPase domain and the HTH (helix-turn-helix) domain, the latter being involved in dimer contacts. Yeast MSH3
[1]
, bacterial proteins involved in DNA mismatch repair, and the predicted protein product of the Rep-3 gene of mouse share extensive sequence similarity. Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein.

References

1.The yeast gene MSH3 defines a new class of eukaryotic MutS homologues. New L, Liu K, Crouse GF. Mol. Gen. Genet. 239, 97-108, (1993). PMID: 8510668

2.Altered dynamics of DNA bases adjacent to a mismatch: a cue for mismatch recognition by MutS. Nag N, Rao BJ, Krishnamoorthy G. J. Mol. Biol. 374, 39-53, (2007). View articlePMID: 17919654

3.The C-terminal region of Escherichia coli MutS and protein oligomerization. Miguel V, Pezza RJ, Argarana CE. Biochem. Biophys. Res. Commun. 360, 412-7, (2007). View articlePMID: 17599803

4.Mismatch repair proteins collaborate with methyltransferases in the repair of O(6)-methylguanine. Rye PT, Delaney JC, Netirojjanakul C, Sun DX, Liu JZ, Essigmann JM. DNA Repair (Amst.) 7, 170-6, (2008). View articlePMID: 17951114

5.Escherichia coli MutS tetramerization domain structure reveals that stable dimers but not tetramers are essential for DNA mismatch repair in vivo. Mendillo ML, Putnam CD, Kolodner RD. J. Biol. Chem. 282, 16345-54, (2007). View articlePMID: 17426027

Further reading

6. Colon cancer and DNA repair: have mismatches met their match? Jiricny J. Trends Genet. 10, 164-8, (1994). View articlePMID: 8036718

7. The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch. Lamers MH, Perrakis A, Enzlin JH, Winterwerp HH, de Wind N, Sixma TK. Nature 407, 711-7, (2000). View articlePMID: 11048711

8. A phylogenomic study of the MutS family of proteins. Eisen JA. Nucleic Acids Res. 26, 4291-300, (1998). View articlePMID: 9722651

9. The origins and early evolution of DNA mismatch repair genes--multiple horizontal gene transfers and co-evolution. Lin Z, Nei M, Ma H. Nucleic Acids Res. 35, 7591-603, (2007). View articlePMID: 17965091

GO terms

cellular component

  • None

Cross References

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