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Damaged DNA and DNA Polymerase III

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DNA polymerase III replicates DNA with incredibly high fidelity. Much of the fidelity of the enzyme comes from the structure of the catalytic pocket, where there is a presynthetic check for base pairing between the template strand and the incoming nucleotide. A side effect of this small binding pocket is the inability of the polymerase to tolerate lesions in which chemical changes have occurred in the base, the deoxyribose sugar, or even the phosphate on the DNA. There are many mechanisms for DNA replication to continue even when a cell is grown under conditions that result in highly damaged DNA. While early work suggested that the polymerization of the leading and lagging strand was so tightly coupled that a lesion on one strand would stop the entire DNA replication fork, more recent work indicates flexibility. It is now clear that although the polymerases producing the leading strand and lagging strand are physically coupled, the two complexes can be momentarily uncoupled by leaving a singlestrand DNA gap at the point of the lesion that blocked one of the DNA polymerases. Other processes can repair these gaps, and in extreme cases, where there is extensive damage in the chromosome, these gaps initiate a DNA damage response called the SOS response (see chapter 10).

Snyder and Champness Molecular Genetics of Bacteria

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