DNA Mismatch Repair: Eukaryotic


In both prokaryotes and eukaryotes, highly‐conserved mismatch‐repair systems both correct DNA replication errors, by coupling recognition of DNA mismatches to identification and excision of the mutated nascent DNA, and interact with recombination mismatches and a variety of DNA lesions. Evolution of single prokaryotic recognition (MutS) and coupling (MutL) proteins into multiple specialized eukaryotic proteins has accompanied expansion of their genomic‐stability functions.

Keywords: genomic stability; error correction; DNA replication; mutagenesis; meiosis

Figure 1.

Evolution and diversification of eukaryotic MSH proteins. Condensed phylogenetic tree derived from alignments of complete amino acid sequences of eight eubacterial MutS and 16 eukaryotic MSH proteins (Culligan et al., ). Each branch (except for Rickettsia prowezekii) corresponds to two or more orthologues.

Figure 2.

Schematic model for ATP‐dependent error correction. MS, MutS (or MutSα, MutSβ) protein; encircled MS, MutS protein in active conformation; fpDNA, homoduplex DNA without mismatches; mmDNA, DNA containing a mismatch; (mm)fpDNA, mismatch‐containing DNA with protein now interacting with its homoduplex region; *, steps that might contribute to the specificity of MMR processing for mmDNA.



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Further Reading

Allen DJ, Malchov A, Grilley M et al. (1997) MutS mediates heteroduplex loop formation by a translocation mechanism. EMBO Journal 16: 4467–4476.

Borts RH, Chambers SR and Abdullah MFF (2000) The many faces of mismatch repair in meiosis. Mutation Research 451: 129–150.

Buermeyer AB, DeschAnes SM, Baker SM and Liskay RM (1999) Mammalian DNA mismatch repair. Annual Review of Genetics 33: 533–564.

Drotschmann K, Clark AB and Kunkel TA (1999) Mutator phenotypes of common polymorphisms and missense mutations in MSH2. Current Biology 9: 907–910.

Fishel R (1998) Mismatch repair, molecular switches, and signal transduction. Genes and Development 12: 2096–2101.

Harfe BD and Jinks‐Robertson S (2000) DNA mismatch repair and genetic instability. Annual Review of Genetics 34: 359–399.

Jiricny J and Nystrom‐Lahti M (2000) Mismatch repair defects in cancer. Current Opinion in Genetics and Development 10: 157–161.

Kolodner RD and Marsischky GT (1999) Eukaryotic DNA mismatch repair. Current Opinion in Genetics and Development 9: 89–96.

Modrich P (1997) Strand‐specific mismatch repair in mammalian cells. Journal of Biological Chemistry 272: 24727–24730.

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Hays, John Bruce(Apr 2001) DNA Mismatch Repair: Eukaryotic. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000570]