DNA Mismatch Repair: Eukaryotic

John Bruce Hays, Oregon State University, Corvallis, Oregon, USA

Published online: April 2001

DOI: 10.1038/npg.els.0000570

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., 2000). Each branch (except for Rickettsia prowezekii) corresponds to two or more orthologues.
Figure 2. Schematic model for ATP-dependent error correction. MS, MutS (or MutS, MutS) 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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 References
    Baker SM, Plug AW, Prolla TA et al. (1996) Involvement of mouse Mlh1in DNA mismatch repair and meiotic crossing over. Nature Genetics 13: 336–342.
    Bjornson KP, Allen DJ and Modrich P (2000) Modulation of MutS ATP hydrolysis by DNA cofactors. Biochemistry 39: 3176–3183.
    Blackwell LJ, Martik D, Bjornson KP, Bjornson ES and Modrich P (1998) Nucleotide-promoted release of hMutS from heteroduplex DNA is consistent with an ATP-dependent translocation mechanism. Journal of Biological Chemistry 48: 32055–32062.
    Culligan KM and Hays JB (2000) Arabidopsis thaliana MutS homologs – atMSH2, atMSH3, atMSH6, and a novel atMSH7 – form three distinct protein heterodimers with different specificities for mismatched DNA. Plant Cell 12: 1–13.
    Culligan KM, Meyer-Gauen G, Lyons-Wilder J and Hays JB (2000) Evolutionary origin, diversification and specialization of eukaryotic MutS-homolog mismatch-repair proteins. Nucleic Acids Research 28: 463–471.
    de Wind N, Dekker M, Berns A, Radman M and te Riele H (1995) Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell 82: 321–330.
    Gradia S, Subramanian D, Wilton T et al. (1999) hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA. Molecular Cell 3: 255–261.
    Iaccarino I, Marra G, Dufner P and Jiricny J (2000) Mutation in the magnesium binding site of hMSH6 disables the hMutS sliding clamp from translocating along DNA. Journal of Biological Chemistry 275: 2080–2086.
    proceedings Nakagawa T, Datta A and Kolodner RD (1999) Multiple functions of MutS- and MutL-related heterocomplexes. Proceedings of the National Academy of Sciences of the USA 96: 14186–14188.
    Umar A, Buermeyer AB, Simon JA et al. (1996) Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell 87: 65–73.
    Wang H, Lawrence CW, Li G-M and Hays JB (1999) Specific binding of human MSH2×MSH6 mismatch-repair protein heterodimers to DNA incorporating thymine- or uracil-containing UV-light photoproducts opposite mismatched bases. Journal of Biological Chemistry 274: 16894–16900.
    proceedings Wang T-F, Kleckner N and Hunter N (1999) Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. Proceedings of the National Academy of Sciences of the USA 96: 8167–8174.
 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.

Related Sub-Topics:

Replication and Recombination | Evolution of Coding and Functional Modules | DNA Damage and Repair | Biomolecular Interactions | Enzymes: Structure and Action Mechanism | Nucleic Acids: Structure, Function, Metabolism
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Article Title: DNA Mismatch Repair: Eukaryotic
 
How to Cite close
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]