Journal article

Human DNA polymerase iota promiscuous mismatch extension.

Vaisman A, Tissier A, Frank E, Goodman M, Woodgate R ...see all

The Journal of biological chemistry, vol. 276, issue 33 (2001) pp. 30615-22

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Abstract

Human DNA polymerase iota is a low-fidelity template copier that preferentially catalyzes the incorporation of the wobble base G, rather than the Watson-Crick base A, opposite template T (Tissier, A., McDonald, J. P., Frank, E. G., and Woodgate, R. (2000) Genes Dev. 14, 1642-1650; Johnson, R. E., Washington, M. T., Haracska, L., Prakash, S., and Prakash, L. (2000) Nature 406, 1015-1019; Zhang, Y., Yuan, F., Wu, X., and Wang, Z. (2000) Mol. Cell. Biol. 20, 7099-7108). Here, we report on its ability to extend all 12 possible mispairs and 4 correct pairs in different sequence contexts. Extension from both matched and mismatched primer termini is generally most efficient and accurate when A is the next template base. In contrast, extension occurs less efficiently and accurately when T is the target template base. A striking exception occurs during extension of a G:T mispair, where the enzyme switches specificity, "preferring" to make a correct A:T base pair immediately downstream from an originally favored G:T mispair. Polymerase iota generates a variety of single and tandem mispairs with high frequency, implying that it may act as a strong mutator when copying undamaged DNA templates in vivo. Even so, its limited ability to catalyze extension from a relatively stable primer/template containing a "buried" mismatch suggests that polymerase iota-catalyzed errors are confined to short template regions.

Author-supplied keywords

  • Base Pair Mismatch
  • Catalysis
  • DNA
  • DNA-Directed DNA Polymerase
  • DNA-Directed DNA Polymerase: metabolism
  • DNA: metabolism
  • Humans

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Authors

  • A Vaisman

  • A Tissier

  • E G Frank

  • M F Goodman

  • R Woodgate

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