Chemistry of Life

Molecular genetics, biochemistry

DNA polymerases

MOLECULAR BIOLOGY: ON DNA POLYMERASES: "Evolution has produced a number of different types of DNA polymerase, but they all have a similar overall three-dimensional shape that has been likened to a right hand, with palm, finger and thumb domains [1]. Polymerases of the A and B families, such as polymerase d, replicate the bulk of genomic DNA during the cell cycle and have been streamlined for processivity and accuracy. These enzymes fit the DNA substrate tightly into their active site, where the replicating base pair is enclosed by the finger domain [2-4]. The mobility of the finger domain underlies a so-called 'induced-fit' mechanism for checking the fidelity of replication: only when an incoming nucleotide forms a perfect Watson-Crick pair with the template base can the fingers close and induce an active conformation of the polymerase. If, nevertheless, an erroneous nucleotide happens to be incorporated, the polymerase responds with conformational distortions of its active center. These induce replication pausing and translocation of the primer terminus towards the intrinsic 'proofreading' exonuclease activity, which removes the mispairing base so that synthesis can resume [5]." O. Fleck and P. Schär (Current Biology 2004 14:R389)5

Carver, T.E.Jr. , Hochstrasser, R.A., and Millar, D.P. (1994). Proofreading DNA: recognition of aberrant DNA termini by the Klenow fragment of DNA polymerase I. Proc. Natl. Acad. Sci. USA 91, 10670-10674

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