Published online 17 May 2006
Article |
RNA aptamers selected against DNA polymerase ß inhibit the polymerase activities of DNA polymerases ß and 
1 Laboratory of Chemical Biology, Department of Pharmacological Sciences, Stony Brook University Stony Brook, NY 11794-8651, USA 2 Institute of Molecular Genetics, Russian Academy of Sciences Moscow 123182, Russia
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Received April 10, 2006. Accepted April 13, 2006.
DNA polymerase ß (polß), a member of the X family of DNA polymerases, is the major polymerase in the base excision repair pathway. Using in vitro selection, we obtained RNA aptamers for polß from a variable pool of 8 x 1012 individual RNA sequences containing 30 random nucleotides. A total of 60 individual clones selected after seven rounds were screened for the ability to inhibit polß activity. All of the inhibitory aptamers analyzed have a predicted tri-lobed structure. Gel mobility shift assays demonstrate that the aptamers can displace the DNA substrate from the polß active site. Inhibition by the aptamers is not polymerase specific; inhibitors of polß also inhibited DNA polymerase 
, a Y-family DNA polymerase. However, the RNA aptamers did not inhibit the Klenow fragment of DNA polymerase I and only had a minor effect on RB69 DNA polymerase activity. Polß and , despite sharing little sequence similarity and belonging to different DNA polymerase families, have similarly open active sites and relatively few interactions with their DNA substrates. This may allow the aptamers to bind and inhibit polymerase activity. RNA aptamers with inhibitory properties may be useful in modulating DNA polymerase actvity in cells.