Researchers from the Superior Council of Scientific Investigations (CSIC) in Spain have demonstrated for the first time that knots are usual in intracellular DNA. These knots can be very harmful for genetic activity and stability. However, the authors of the study show that there are mechanisms that minimize the degree of DNA knotting to allow proper chromosome conformation and dynamics.

The long DNA molecules fold in a hierarchical way to keep the spatial organization of the genome within the cell nucleus. First, segments of DNA twist regularly on histones octamers to form nucleosomes. Nucleosome chains longitudinally compact to form chromatin fibers; which in turn super-twist and fold creating handles, to shape chromosomes.

The research found that enzymes called topoisomerases have an essential role during condensation and decondensation processes of nucleosome chains and chromatin fibers.

Topoisomerase eliminate topological problems (tensions, knots, chains) arising between different segments of DNA molecules. In particular, topoisomerase II produces transient cuts in the DNA double helix, allowing segments of DNA passing through each other, as magicians do when they unite or separate two metal rings.

While topoisomerase II is capable of removing the topological problems of DNA, the enzyme can also cause the formation of knots when the DNA molecules are condensed into chromatin fibers,” explains study director Joaquim Roca, researcher the CSIC’s Institute of Molecular Biology of Barcelona​​. “Therefore, there is a balance between the formation and elimination of knots, that cells must regulate to prevent that its entire DNA becomes a huge entanglement of filaments,” he added.

Another interesting aspect of this research is that the analysis of the knots formed in intracellular DNA allows deducing structural properties of in vivo chromatin. “The abundance and type of nodes we observed indicate that nucleosomes chains are very flexible, and chromatin fibers are formed by irregular aggregates of nucleosomes that repeat periodically,” said Roca.


Source: Agencia ID