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IPR036187

DNA mismatch repair protein MutS, core domain superfamily

InterPro entry
Short nameDNA_mismatch_repair_MutS_sf
Overlapping entries
 

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
[5]
. 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
[4]
. 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
[2]
. MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level
[3]
. 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.

The core domain of MutS adopts a multi-helical structure comprised of two subdomains, which are interrupted by the clamp domain. Two of the helices in the core domain comprise the levers that extend towards the DNA. This domain is found associated with Pfam:PF00488, Pfam:PF05188, Pfam:PF01624 and Pfam:PF05190. The aligned region corresponds with domain III, which is central to the structure of Thermus aquaticus MutS
[1]
.

References

1.Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA. Obmolova G, Ban C, Hsieh P, Yang W. Nature 407, 703-10, (2000). View articlePMID: 11048710

2.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

3.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

4.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

5.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

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

8. 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

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

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