Base pairs proof-reading

The 3 -+5 exonuclease activity plays an important role in polymerization in proof reading the base pair formed at each polymerization step. The enzyme checks the nature of each base-paired primer terminus before the polymerase proceeds to add the next nucleotide to the primer. It thus supplements the capacity of the polymerase to match the incoming nucleotide substrate to the template. A mismatched terminal nucleotide on the primer activates a site on the enzyme which results in the hydrolysis of the phosphodiester bond and the removal of the mismatched residue. The function of this 3 - 5 exonuclease activity is therefore to recognize and cleave incorrectly or non-base paired residues at the 3 -end of DNA chains. It will therefore degrade single stranded DNA and frayed or non-base paired residues at the ends of duplex DNA molecules provided they terminate in a 3 -hydroxyl group. 

The virtuosity of the DNA polymerase first isolated from E. coli still amazes me. Holding one or two turns of one chain of DNA helix as template, it assembles a complementary chain thousands of nucleotides long. It does so by Watson-Crick base pairing with an accuracy which exceeds chemical predictions. The enzyme achieves this fidelity of replication by a proof-reading exonuclease in its active center. This 3 5 exonuclease... 

DNA replication involves a highly developed enzymatic machinery which uses a proof reading mechanism in order to increase the single digit accuracy. Thereby, genomes as long as some million base pairs become possible. In procaryotes nature again seems to operate close to the error limit. Bacteria, nevertheless, have retained a certain flexibility to adjust mutation rates to the evolutionary needs of the moment. They do not seem to replicate as closely to the accuracy limit as viruses do. 

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