an asymmetric dimer with DNA polymerase delta.) Proof-reading and error correction Although rare, incorrect base pairing polymerisation does occur during chain elongation. (The structure and chemistry of replicative polymerases mean that errors are unlikely, but they do occur.) Many replicative polymerases contain an "error correction" mechanism in the form of a 3' to 5' exonuclease domain that is capable of removing base pairs from the exposed 3' end of the growing chain. Error correction is possible because base pair errors distort the position of the magnesium ions in the polymerisation sub-unit, and the structural-chemical distortion of the polymerisation unit effectively stalls the polymerisation process by slowing the reaction. Subsequently, the chemical reaction in the exonuclease unit takes over and removes nucleotides from the exposed 3' end of the growing chain. Once an error is removed, the structure and chemistry of the polymerisation unit returns to normal and DNA replication continues. Working collectively in this fashion, the polymerisation active site can be thought of as the "proof-reader", since it senses mismatches, and the exonuclease is the "editor", since it corrects the errors. Base pair errors distort the polymerase active site for between 4 and 6 nucleotides, which means, depending on the type of mismatch, there are up to six chances for error correction. The error sensing and error correction features, combined with the inherent accuracy that arises from the structure and chemistry of replicative polymerases, contribute to an error rate of approximately 1 base pair mismatch in 108 to 1010 base pairs. Errors can be classified in three categories: purine-purine mismatches, pyrimidine-pyrimidine mismatches, and pyrimidine-purine mismatches. The chemistry of each mismatch varies, and so does the behaviour of the replicative polymerase with respect to its mismatch sensing activity. The replication of bacteriophage T4 DNA upon infection of E. coli is a well-studied DNA replication system. During the period of exponential DNA increase at 37°C, the rate of elongation is 749 nucleotides per second. The mutation rate during replication is 1.7 mutations per 108 base pairs. Thus DNA replication in this system is both very rapid and highly accurate. Primer removal and nick ligation There are two problems after leading and lagging strand synthesis: RNA remains in the duplex and there are nicks between each Okazaki fragment in the lagging duplex. These problems are solved by a variety of DNA repair enzymes that vary by organism, including: DNA polymerase I, DNA polymerase