The catalytic core of
human topoisomerase IIα preferentially
cleaves negatively supercoiled DNA in the presence of etoposide and
CP-115,953. The ability of wild-type topoisomerase IIα (WT,
black) and the catalytic core (CC, red) to cleave negatively [(−)SC,
filled circles] or positively [(+)SC, empty circles] supercoiled plasmid
DNA in the presence of etoposide (left) or CP-115,953 (right) is shown.
Results for CP-115,953 are not shown at concentrations above 10 μM
with the wild-type enzyme because the drug induced multiple cleavage
events per plasmid. The inset shows cleavage induced by the catalytic
core in the presence of 250 μM etoposide. Error bars represent
the standard deviation of at least three independent experiments.