Eukaryotic mismatch repair

Modrich P. Mechanisms in eukaryotic mismatch repair. J. Biol. Chem. 2006 281 30305-30309. 

Mismatched base pairs can arise from errors that occur during recombination repair. A variety of prokaryotic and eukaryotic mismatch repair proteins repair mismatched base pairs by a variety of mechanisms that involve the excision of one of the bases [69, 70]. 

Kolodner, R. (1996) Biochemistry and genetics of eukaryotic mismatch repair. Gems Dev. 10 1433. 

See also Postreplication Repair, Recombinational Repair, Prokaryotic Mismatch Repair, Eukaryotic Mismatch Repair, SOS Regulon (from Chapter 26)... 

See also Eukaryotic Mismatch Repair, Postreplication Repair... 

Nucleotide Chemistry The cells of many eukaryotic organisms have highly specialized systems that specifically repair G-T mismatches in DNA The mismatch is repaired to form a G=C (not A=T) base pair. This G-T mismatch repair mechanism occurs in addition to a more general system that repairs virtually all mismatches. Can you suggest why cells might require a specialized system to repair G-T mismatches ... 

Culligan KM, Meyer-Gauen G, Lyons-Weiler J, Hays JB (2000) Evolutionary origin, diversification and specialization of eukaryotic MutS homolog mismatch repair proteins. Nucleic Acids Res 28 463-471... 

Eukaryotic cells have three excIsIon-repalr systems for correcting mispalred bases and for removing UV-Induced thymine-thymine dimers or large chemical adducts from DNA. Base excision repair, mismatch repair, and nucleotide excision repair operate with high accuracy and generally do not introduce errors. 

Mismatch repair (prokaryotic or eukaryotic), a process that recognizes DNA mismatches created either by replication errors, non-homologous recombination, or damage to one DNA base, and corrects the error. 

Answer Many C residues of CpG sequences in eukaryotic DNA are methylated at the 5 position to 5-methylcytosine. (About 5% of all C residues are methylated.) Spontaneous deamination of 5-methylcytosine yields thymine, T, and a G-T mismatch resulting from spontaneous deamination of 5-methylcytosine in a G=C base pair is one of the most common mismatches in eukaryotic cells. The specialized repair mechanism to convert G-T back to G=C is directed at this common class of mismatch. 

Methylation underlies several important biological processes, including restriction and modification, mismatch error correction (a DNA repair process), and the control of eukaryotic gene expression. S-Adenosylmethionine (AdoMet) is the substrate for methylation of both RNA and DNA. Methylation occurs at the polynucleotide level, with transfer of a methyl group from AdoMet to a nucleotide residue. 

Additional activities that occur during replication include proofreading and DNA repair. Pol 8, which is part of the replication complex, has the 3 5 -exonuclease activity required for proofreading. Enzymes that catalyze repair of mismatched bases are also present (see section III.B.3 of this chapter). Consequently, eukaryotic replication occurs with high fidelity approximately one mis-pairing occurs for every 10 to 10 nucleotides incorporated into growing DNA chains. 

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