title: Human DNA polymerase iota promiscuous mismatch extension.
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.
authors.affiliation: Section on DNA Replication, Repair, and Mutagenesis, NICHD, National Institutes of Health, Bethesda, Maryland 20892-2725, USA.
authors.forename: A
authors.initials: A
authors.lastname: Vaisman
authors.forename: A
authors.initials: A
authors.lastname: Tissier
authors.forename: E G
authors.initials: EG
authors.lastname: Frank
authors.forename: M F
authors.initials: MF
authors.lastname: Goodman
authors.forename: R
authors.initials: R
authors.lastname: Woodgate
mesh_terms: D020137:Base Pair Mismatch; D002384:Catalysis; D004247:DNA / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D000094769:DNA Polymerase iota
chemical_list: D004247:DNA; D004259:DNA-Directed DNA Polymerase; D000094769:DNA Polymerase iota; C000722070:POLI protein, human