Departments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901, USA
By uncoupling the cleavage and ligation reactions of DNA oligonucleotides
mediated by topoisomerase I, it has been possible to demonstrate
modification of DNA oligonucleotide structure by the enzyme.
These modifications indicate an unusual flexibility inherent
in the behavior of topoisomerase I and may reflect some of the
cellular roles played by the enzyme. The ability of individual
camptothecin analogues to inhibit these modification processes
differentially provides insight into the relative nature of
the microenvironments present. To the extent that these enzyme-mediated
structural modifications do constitute models of cellular roles
for the enzyme, the observed differential inhibition also provides
a potential strategy for assessing the function and importance
of such modifications.
