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, to be published by Nature in advance on the Internet on Sunday, June 24, is supported by the Foundation for Fundamental Research on Matter and the Netherlands Organisation for Scientific Research.
Frank Nuijens | alfa
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy