A particular type of cancer drug works in a previously unexpected way, suggests a Nature paper published online.
Topoisomerase inhibitors, such as topotecan, are a class of anti-cancer drugs that act on proteins that relax a form of built-up stress in DNA called supercoiling.
It's thought that they act by stabilizing a covalent complex between the topoisomerase enzyme and DNA, which then sets up a road-block to the DNA replication machinery triggering cell death.
Nynke H Dekker and colleagues look at single topoisomerase molecules 'in the act'. They find that the inhibitors don't just stabilize an intermediate but actually affect the ability of topoisomerase to relax DNA supercoiling, suggesting a new mechanism by which these drugs cause cytotoxicity.
Nynke H Dekker (Delft University of Technology, Netherlands)
Daniel A Koster (Delft University of Technology, Netherlands)
(C) Nature press release.
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