A paper by UAB professor Joan-Ramon Daban analyzes in depth the physical problems associated with DNA packaging that are often neglected in structural models of chromosomes. The study published in the journal Small structures shows that the multilaminar organization of DNA, proposed on the basis of previous experimental research conducted at UAB, is fully compatible with the structural and functional properties of chromosomes. This organization can be explained by weak interactions between nucleosomes, the repetitive blocks that fold the DNA double helix.
The enormously long genomic DNA molecules in eukaryotic organisms must be tightly folded to fit the micrometric dimensions of the chromosomes compressed during mitosis to protect the genetic information before cell division. Histone proteins were selected early in evolution to transform DNA into chromatin filaments formed by many nucleosomes. The central part of each nucleosome (core particle) is a cylindrical structure (5.7 nanometers high and 11 in diameter) formed by approximately two turns of DNA (147 base pairs) wrapped around an octamer of histones. Understanding the folding mechanism that leads to high compaction of the chromatin filaments in chromosomes has been a major scientific challenge for decades.
A physically consistent and realistic structural model for DNA organization in chromosomes must be compatible with all constraints imposed by the observed structural and functional properties of chromosomes. It must be compatible with the high concentration of DNA and the elongated cylindrical shape of chromosomes and the known self-associative properties of chromatin, as well as with effective protection of chromosomal DNA against topological entanglement and mechanical breakage. Unfortunately, these limitations are not taken into account in the various models proposed based on the results obtained with various experimental techniques and computer modeling studies.
In the laboratory of Professor Joan-Ramon Daban, from UAB’s Department of Biochemistry and Molecular Biology, researchers had previously used transmission electron microscopy, atomic force microscopy and cryo-electron tomography techniques and observed that the chromatin originated from chromosomes prepared in Metaphase ionic conditions form flat multilayer plates, in which each layer has the thickness corresponding to a mononucleosome layer. Based on these results, the UAB researchers propose that the chromatin filament of the chromosomes folds in a regular pattern formed by many layers stacked on top of each other along the axis of the chromosome. This multi-layer model is compatible with all structural constraints considered above. Moreover, it justifies the geometry of chromosome bands and translocations observed in cytogenetic analyses, and is compatible with feasible physical mechanisms for the control of gene expression, as well as for DNA replication, repair, and segregation to daughter cells.
Chromosomes can be regarded as self-organized liquid crystals
Nucleosomes are repetitive building blocks introduced into the monotonic linear structure of double-helical DNA. It has been shown in several laboratories that isolated nucleosome core particles have a high tendency to interact face to face, forming large columnar structures. Presumably, according to the properties of soft matter systems, the interplay of these weak anisotropic interactions between nucleosomes and thermal energy could be responsible for the formation of these columnar structures. In the multilayer chromosome model, the repetitive weak interaction between nucleosomes causes the stacking of many chromatin layers. These low-energy interactions at the nanoscale justify the self-organization of entire chromosomes, which can be regarded as lamellar liquid crystals, internally cross-linked by the covalent backbone of a single DNA molecule.
The spontaneous formation of well-defined three-dimensional patterns is consistent with contemporary research in nanoscience and nanotechnology that has yielded many impressive structures of different sizes, themselves composed of various biological and synthetic repetitive building blocks. Professor Daban believes that molecular biology has discovered the self-assembly of various biomolecular structures, but currently the research on the self-organization of soft matter systems is mainly developed in the field of nanotechnology.
The article was published in the interdisciplinary journal Small structures, who is interested in microstructures built from nanoparticles, from the point of view of both nanotechnology and life sciences.
