An international team, led by researcher Joaquim Roca, head of the Dept. of Molecular and Cellular Biology of the lnstitut de Biologia Molecular de Barcelona (IBMB-CSIC), which is associated with the PCB, has discovered that highly complex knots can be formed in DNA. In their analysis of these knots, the authors have been able to deduce how DNA folds inside the chromosomes. The results of this study have been published in this week's edition of the scientific journal "Proceedings of the National Academy of Sciences USA" (PNAS).

DNA molecules, the longitude of which is enormous in comparison with their diameter, are highly condensed and packed in a tiny space, namely the chromosomes. To give an idea, if you were to take out and unravel the DNA from a human cell, it would reach a length of 2 metres. Therefore, to fit into such a reduced space, DNA folds in each of the 46 chromosomes held in a human cell.

“It has never been possible to study how DNA folds; and this has been one of the pressing enigmas in biology “, explained Joaquim Roca. These folds, or expressed in another way, the special trajectory that DNA takes within chromosomes had until now gone undetected by methods designed for structural analysis. One solution to this problem could be achieved from the analysis of knots, as these researchers propose in their study. DNA molecules can be highly knotted. In fact, all cells have several enzymes, the topoisomerases, which regulate DNA knotting.

There is an infinite number of distinct knot types. Given that the identity of a knot does not change even if its shape is altered, each knot acts as a memory of the trajectory from which it originated. At present, using electrophoresis, it is possible to identify the types of knots formed in DNA. Furthermore, using computational techniques, the trajectories that facilitate (or not) the formation of certain knot types can be simulated. By comparing the knot distributions obtained by these two techniques, the authors of this study have demonstrated that DNA in the chromosome of certain viruses fold to form a tangle with a high writhe bias. These researchers have established a correlation between knot type and DNA arrangement, thereby one value can be inferred from the other. For example, in the viral DNA analysed, one type of knot predominates over others. The same principle could be applied to cellular chromosomes.

This is the first topologic demonstration that DNA is not organized in a chaotic and random fashion inside a chromosome, but that its organisation is subjected to precision. It is also the first method that has allowed researchers to deduce the way in which DNA filaments are organized in the three-dimensional structure of chromosomes.