Etoposide
quinone is a covalent poison of topoisomerase IIβ.
In the left panel, etoposide quinone enhancement of DNA cleavage is
not reversed by the addition of reducing agents after DNA cleavage
complexes have been established. DNA cleavage reactions were carried
out in the absence (blue bars) or presence (open blue bars) of DTT.
Reaction mixtures contained no drug (ND) or 30 μM etoposide
quinone in mixtures that included DTT at the time of DNA cleavage
(Pre EQ) or DTT that was added (for an additional 6 min) after cleavage
complexes were formed (Post EQ). In the right panel, etoposide quinone
does not form DNA lesions that poison topoisomerase IIβ. DNA
was incubated without (−EQ, open orange bars) or with (+EQ,
orange bars) 30 μM etoposide quinone. DNA was purified from
free drug and used in DNA cleavage reactions mediated by topoisomerase
IIβ. DNA cleavage reactions were performed in the absence of
drug (ND) or in the presence of 30 μM etoposide quinone (EQ).
In all cases, error bars represent the standard deviation of three
independent experiments.