Postreplication mismatched repair

Postreplicational mismatch repair has been found to correct errors in base substitution occurring during DNA replication in prokaryotes.48 This lowers the error rate for the polymerase from 1 in 106 to 107 to the observed range of values of 1 in 108 to 1010 in E. coli. How does the repair system know in this case which base in a mispair is the incorrect one The answer appears to be that the parent strand is tagged by methylation. A small proportion, some 0.2%, of the cytosine residues are methylated at the 5 position, and a similar proportion of the adenine residues are methylated at the 6 position. As methylation is a postreplicative event, the daughter strand is temporarily undermethylated after replication. 

Why is the editing mechanism of the polymerase unable to achieve the necessary accuracy by itself why does it need the postreplicative mismatch repair mechanism The answer comes from analyzing the cost of editing. 

After replication, other mechanisms replace mismatched bases that escaped proofreading so that the fidelity of DNA replication is very high. The two processes of proofreading and postreplication mismatch repair result in an overall error rate of about 10 °, that is, less than one mismatched base pair in 10 billion. 

Procarbazine and the triazenes dacarbazine and temozolomide act by different mechanisms, but they all exert an antineoplastic effect through the 0 -methylation of guanine nucleotides. 0 -methylguanine pairs preferentially with thymine, and these mispairs prompt point mutations during subsequent DNA replication cycles and trigger cell destruction through the activation of the normal postreplication mismatch repair (MMR)... 

As illustrated by the model (Fig. 3), postreplicative mismatch repair also appears to play a role in the SHM process at A/T base pairs. Mice deficient in the MutS homologs (Msh) 2 or Mshfi have fewer mutations... 

Enhanced tolerance to DNA adducts has been fonnd in some cisplatin-resistant ceUs. Mechanisms that are involved are enhanced postreplicative bypass the ability of the replication complex to synthesize DNA downstream a cisplatin-indnced lesion and defects in the repair process named mismatch repair (MMR). 

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

Another postreplication repair system is that of mismatch repair, which can repair replication mistakes that escape proofreading or which arise from chemical alteration of bases, such as deamination of cytosine to form uracil. 

See also Eukaryotic Mismatch Repair, Postreplication Repair... 

Postreplication repair refers to processes that attempt to fix mismatches, gaps, or damage to DNA that escape the repair processes that occur during replication (such as proofreading—see here). 

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