Competitive inhibition of uracil DNA glycosylase by a modified nucleotide whose triphosphate is a substrate for DNA polymerase.

Abstract:

Base excision repair (BER) enzymes are attractive targets for antiviral and anticancer agents. A number of nucleotides and nucleotide analogues are potent competitive inhibitors of BER glycosylases when they are incorporated into synthetic oligonucleotides. However, these molecules often are not substrates for DNA polymerases, which limits their utility in cells and as potential therapeutic agents. 1'-Cyano-2'-deoxyuridine (CNdU) is a nanomolar competitive inhibitor of uracil DNA glycosylase. In addition, the respective nucleotide triphosphate is accepted as a substrate by the Klenow fragment (exo(-)) of DNA polymerase I from E. coli. This is the first competitive inhibitor of UDG that is incorporated into DNA by Klenow exo(-), a model replicative polymerase. 1'-Cyano-2'-deoxyuridine (CNdU) and related molecules may prove useful as a new family of therapeutic or experimental agents that target DNA repair by using the cells' polymerase(s) to incorporate them into DNA. A potential benefit of such a mechanism is that multiple incorporations can occur for longer DNA molecules leading to amplification of the inhibitory effect beyond that seen here with short DNA duplexes.

Polymerases:

Topics:

Status:

new topics/pols set partial results complete validated

Results:

No results available for this paper.

Entry validated by:

Log in to edit reference All References

Using Polbase tables:

Sorting:

Tables may be sorted by clicking on any of the column titles. A second click reverses the sort order. <Ctrl> + click on the column titles to sort by more than one column (e.g. family then name).

Filtering:

It is also possible to filter the table by typing into the search box above the table. This will instantly hide lines from the table that do not contain your search text.