New optical tweezers unravel DNA bacteria
Researchers at the Vrije Universiteit, led by Dr. G.J.L. Wuite, have succeeded in literally unravelling bacterial chromosomes furthermore by using an optical micro tweezer. They demonstrated that (and how) an important protein, called H-NS, binds bacterial DNA strands. By using this technology, for the first time it is now possible to prove that seemingly chaotic balls of DNA bacteria, are actually neatly organized and can function dynamically. Moreover, the H-NS protein that binds the DNA strands, is a possible new point of departure for developing medicines fighting pathogenetic bacteria. The results of this research, also with funding of the FOM Foundation, have been published in the scientific journal Nature on 16 November 2006.
Unlike cells in the human body, bacteria do not have cell nuclei. These micro organisms are less complex than the human body cells, which makes it, surprisingly, more difficult to uncover how the DNA in a bacterium cell is being organized. Prior to the use of the optical tweezer, scientists were not quite able to identify and investigate the three-dimensional organization of the bacterial DNA.
In human as well as in animal cells, DNA strands are rolled into chromosomes and they are extremely well organized. The bacterial chromosome is much more dynamically folded into a small group of proteins that binds the DNA non-specifically. Consequently, these proteins have several, overall functions. The DNA is not very organized, like a ball of noodles in the cell - at least, so it seems.
For fission or repair the bacteria must double its DNA, which cannot be done without organization and direction. The DNA doubling occurs (among others) as a result of the so-called motor proteins: they move along the DNA and replicate every nucleotide in the DNA order. It was already known that certain proteins prevented the balls of DNA from entangling; but it was not known how it was possible for a motor protein to move along the DNA strands. This mystery has now been solved.
First of all, the researchers have now been demonstrated that a specific protein (namely, histone-like nucleod structuring protein, H-NS) binds two strands of DNA. H-NS is a small protein that has a kind of little ball on both ends and is able to bind to DNA, because it fits in the DNA helix, in the cavities along the helix's revolving spiral staircase structure. Remus Dame: "It is fine that the measurements have also shown the helix shape of DNA. But it is much more important that we were able to measure the strength that will bind H-NS to DNA." This strength appears to be weak: each arm of H-NS is loosely bound to a DNA helix.
Besides, the bond is unstable: one arm of H-NS will just come off for a certain period of time and subsequently will attach on the DNA again. The functioning of bonding will not be hindered if each of the proteins will come off and attach again every now and then, because there are a lot of H-NS proteins between the two parallel DNA helixes. Gijs Wuite: "And this explains exactly why motor proteins will not be hindered by H-NS when they have to move along the DNA: these proteins exert a much higher strength and the H-NS just let them pass. This has not been demonstrated ever before."
The article is entitled 'Bacterial chromatin organization by H-NS protein unravelled using dual DNA manipulation'. It will be published in Nature on 16 November 2006. The authors are Gijs Wuite, Remus Dame and Maarten Noom.
For more information, please contact Gijs Wuite, Vrije Universiteit, phone +31 (0)20 598 79 87.