8-methoxycaffeine inhibition of Drosophila DNA topoisomerase II.
We have investigated the effect of 8-methoxycaffeine on the interaction between Drosophila DNA topoisomerase II and DNA. We have shown that 8-methoxycaffeine affected the enzyme strand-passing activity by inhibiting decatenation of kinetoplast DNA, and that it interfered with the breakage-reunion reaction by stabilizing a cleavable complex. Treatment of the cleavable complex with protein denaturant resulted in DNA breaks. High resolution mapping of the cleavage sites in the central spacer region of Tetrahymena rDNA revealed that, contrary to what was observed with clinically important DNA topoisomerase II inhibitors, 8-methoxycaffeine did not modify the cleavage pattern observed without the drug.
Tornaletti
S
S
Istituto di Genetica Biochimica ed Evoluzionistica del C.N.R., Pavia, Italy.
Andersen
A H
AH
Christiansen
K
K
Pedrini
A M
AM
D000818:Animals; D001665:Binding Sites; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004330:Drosophila / Q000187:drug effects* / Q000201:enzymology; D059005:Topoisomerase II Inhibitors
D059005:Topoisomerase II Inhibitors; D002110:Caffeine; C066637:8-methoxycaffeine