A TopoisomeraseIB protein (green) is hindered in unwinding DNA loops by the cancer inhibitor topotecan (red). The DNA polymerase protein (grey), a protein which duplicates DNA, is hindered by the DNA loops.
Credit: Delft University of Technology / Tremani
Researchers in Delft University of Technology's Kavli Institute of Nanoscience in The Netherlands have cast new light on the workings of the important cancer inhibitor topotecan. Little had been known about the underlying molecular mechanism, but the Delft scientists can now view the effects of the medicine live at the levelin of a single DNA molecule.
The medicine investigated, topotecan, 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 Delft researchers have now discovered to their surprise 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.
PhD candidate Daniel Koster, Master's student Elisa Bot and researcher Nynke Dekker of the Molecular Biophysics group of the Kavli Institute of Nanoscience Delft have managed to unravel this mechanism in an extremely direct manner. In the laboratory they fixed a single DNA molecule between a glass plate and a magnetic sphere. With the help of two magnets they could both pull and twist the DNA molecule.
When they added TopoIB to a twisted piece of DNA, they saw that the loops were slowly removed. What is exceptional is that the action of one TopoIB enzyme on one DNA molecule could be observed live. In collaboration with St. Jude Children's Research Hospital Memphis (USA) the mechanism could also be observed in living yeast cells.
The research was published in the journal Nature (June 24). The lead author of the article, Daniel Koster, will receive his PhD at TU Delft partly on the results described in the article. The research is supported by the Foundation for Fundamental Research on Matter and the Netherlands Organisation for Scientific Research.
TU DElft - Delft Research Centres
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10 comments:
I LOVE your blog... it helps me show off my super cool new knowledge about stuff.... :)
q- you have been holding out on me!!! i love the space stuff- and now i get to look this one over! good deal!
as for pres- no thanks :) hubby wants that job. perhaps i should do something to shed the laura bush first lady position :)
lol Random,
I'm having fun and enjoying myself round your place too
Hi Betmo,
how can you not want the job
With such firm convictions
you'd make an excellent President.
Not sure about the first lady role
This is good to hear Quasar! Thank you!
They look like funny weird little bugs? Woo Hoo if they gobble on cancer ... bring on the bugs!
Hi Katie, do you think it is man's destiny to beat every illness and every disease.
Hi Aggie, do you think it is man's destiny to beat every illness and every disease. Is it all just random or is it fate. Or is it all just Random Fate?
I think it is mans "challenge" to overcome ... but if man were to fail and die out, then nature would find a way to "bug" the hell out of illness and disease and regain paradise.
lol Aggie,
so maybe paradise is only possible without human failings, weaknesses or disease
or rather Paradise is the absence of human failings, weakness & disease
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