DNA Mismatch Repair

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General Description

"A system for the correction of errors in which an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. The mismatch repair system promotes genomic fidelity by repairing base-base mismatches, insertion-deletion loops and heterologies generated during DNA replication and recombination." [ISBN:0198506732 "Oxford Dictionary of Biochemistry and Molecular Biology"]

Corrects mismatched and unpaired bases arising from:

  • Replication Errors
  • Physical Damage to Bases
  • Homologous Recombination

Review Articles[1]

Components

Function

Regulation

Cell Biology

  • Recognition of a Mismatch[7][8]
    • MutS binds DNA non-specifically and bends it in search of a mismatch
    • MutS undergoes a conformation change when bound to a mismatched duplex to form an initial recognition complex (DNA is kinked)
    • MutS undergoes a further conformation change to a final recognition complex (DNA is unbent)


  • Excision of the Mismatch
    • MutH endonuclease is activated by MutS, MutL, ATP, Mg2+, and a mismatched piece of DNA[9]
    • Mismatch repair excision is bidirectional[10][11]

Experimental Resources

Comparison with other Organisms

Notes

Related GO Terms

References

  1. ↑ Modrich, P & Lahue, R (1996) Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu. Rev. Biochem. 65 101-33 PubMed
  2. ↑ Lahue, RS et al. (1987) Requirement for d(GATC) sequences in Escherichia coli mutHLS mismatch correction. Proc. Natl. Acad. Sci. U.S.A. 84 1482-6 PubMed
  3. ↑ Parker, BO & Marinus, MG (1992) Repair of DNA heteroduplexes containing small heterologous sequences in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 89 1730-4 PubMed
  4. ↑ Su, SS & Modrich, P (1986) Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs. Proc. Natl. Acad. Sci. U.S.A. 83 5057-61 PubMed
  5. ↑ Hall, MC & Matson, SW (1999) The Escherichia coli MutL protein physically interacts with MutH and stimulates the MutH-associated endonuclease activity. J. Biol. Chem. 274 1306-12 PubMed
  6. ↑ Spampinato, C & Modrich, P (2000) The MutL ATPase is required for mismatch repair. J. Biol. Chem. 275 9863-9 PubMed
  7. ↑ Wang, H et al. (2003) DNA bending and unbending by MutS govern mismatch recognition and specificity. Proc. Natl. Acad. Sci. U.S.A. 100 14822-7 PubMed
  8. ↑ Smith, J & Modrich, P (1996) Mutation detection with MutH, MutL, and MutS mismatch repair proteins. Proc. Natl. Acad. Sci. U.S.A. 93 4374-9 PubMed
  9. ↑ Au, KG et al. (1992) Initiation of methyl-directed mismatch repair. J. Biol. Chem. 267 12142-8 PubMed
  10. ↑ Cooper, DL et al. (1993) Methyl-directed mismatch repair is bidirectional. J. Biol. Chem. 268 11823-9 PubMed
  11. ↑ Grilley, M et al. (1993) Bidirectional excision in methyl-directed mismatch repair. J. Biol. Chem. 268 11830-7 PubMed
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