Topotecan, a cancer inhibitor, interacts with an important protein (TopoIB), causing a (cancer) cell to malfunction. The TopoIB protein is responsible for the removal of loops from DNA, which arise amongst other things during cell division.
The TopoIB protein binds to the DNA molecule, clamps around it and cuts one of the two DNA strands, after which it allows it to unwind and finally joins the broken ends together.
Until now it has been supposed that topotecan only causes the TopoIB protein to reside longer than normal on the DNA molecule, disturbing the cell division and damaging the (cancer) cell. But the researchers at the University of Delft have now discovered that adding topotecan also dramatically impedes the unwinding and that DNA loops accumulate as a result. The accumulation of these DNA loops forms the basis for an alternative mechanism, and could help in the development of better cancer medicine.