[Home]   [Full version]  

Scientists track the influence of a cancer inhibitor on a single DNA molecule

Jun 25 ,Medicine & Health


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 research is being published this week in the journal Nature. The lead author of the article, Daniel Koster, will receive his PhD at TU Delft on Monday June 25, partly on the results described in the article.

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.

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.

Source: Delft University of Technology

Related stories:

Real-time observation of the DNA-repair mechanism
For the first time, researchers at Delft University of Technology have witnessed the spontaneous repair of damage to DNA molecules in real time. They observed this at the level of a single DNA molecule. Insight into this type of repair mechanism is essential as errors in this process can lead to the development of cancerous cells. Researchers from the Kavli Institute of Nanoscience Delft are to publish an article on this in the leading scientific journal Molecular Cell.
Nanotweezers Unlock Anticancer Drug Secrets
The annoying bulges of an overwound telephone cord that shorten its reach and limit a caller’s motion help explain why drugs called camptothecins are so effective in killing cancer cells, according to investigators led by Mary-Ann Bjornsti, Ph.D., at St. Jude Children’s Research Hospital, and Nynke Dekker, Ph.D., at Delft Technology University.
Tiny tweezers and yeast help researchers show how cancer drug works
The annoying bulges of an over-wound telephone cord that shorten its reach and limit a caller’s motion help to explain why drugs called camptothecins are so effective in killing cancer cells, according to investigators at St. Jude Children's Research Hospital and Delft University of Technology.
Nanotechnology meets biology and DNA finds its groove
Pity the molecular biologist.The object of fascination for most is the DNA molecule. But in solution, DNA, the genetic material that hold the detailed instructions for virtually all life, is a twisted knot, looking more like a battered ball of yarn than the famous double helix. To study it, scientists generally are forced to work with collections of molecules floating in solution, and there is no easy way to precisely single out individual molecules for study.
Sperm Whales in Gulf Seemingly Unaffected by Distant Seismic Sounds
A six-year study on sperm whales in the Gulf of Mexico – designed to learn more about their abundance, migration patterns and behavior – suggests that long-range seismic sounds associated with oil and gas exploration and production don’t significantly affect the whales’ movement at distances greater than five kilometers, or about three miles.
Tahitian vanilla originated in Maya forests
The origin of the Tahitian vanilla orchid, whose cured fruit is the source of the rare and highly esteemed gourmet French Polynesian spice, has long eluded botanists. Known by the scientific name Vanilla tahitensis, Tahitian vanilla is found to exist only in cultivation; natural, wild populations of the orchid have never been encountered.
Accumulated bits of a cell's own DNA can trigger autoimmune disease
A security system wired within every cell to detect the presence of rogue viral DNA can sometimes go awry, triggering an autoimmune response to single-stranded bits of the cell's own DNA, according to a report in the August 22nd issue of the journal Cell, a Cell Press publication. The source of that single-stranded DNA is so-called endogenous retroelements—genetic elements accounting for a substantial portion of the genome that can move to new locations using a "copy and paste" mechanism, according to the researchers.
Exploding chromosomes fuel research about evolution of genetic storage
Human cells somehow squeeze two meters of double-stranded DNA into the space of a typical chromosome, a package 10,000 times smaller than the volume of genetic material it contains.

News discussion:

Medicine & Health news

[Home]   [Full version]