The three dimensional organization of genomes remains mostly unknown due to their high degree of condensation. Biophysical studies predict that condensation promotes the topological entanglement of chromatin fibers and the inhibition of function. How organisms balance between functionally active genomes and a high degree of condensation remains to be determined. Here we hypothesize that the Rabl configuration, characterized by the attachment of centromeres and telomeres to the nuclear envelope, helps to reduce the topological entanglement of chromosomes. To test this hypothesis we developed a novel method to quantify chromosome entanglement complexity in 3D reconstructions obtained from Chromosome Conformation Capture (CCC) data. Applying this method to published data of the yeast genome, we show that computational models implementing the attachment of telomeres or centromeres alone are not sufficient to obtain the reduced entanglement complexity observed in 3D reconstructions. It is only when the centromeres and telomeres are attached to the nuclear envelope (i.e. the Rabl configuration) that the complexity of entanglement of the genome is comparable to that of the 3D reconstructions. We therefore suggest that the Rabl configuration is an essential player in the simplification of the entanglement of chromatin fibers.

Molecular motors that translocate DNA are ubiquitous in nature. During morphogenesis of double-stranded DNA bacteriophages, a molecular motor drives the viral genome inside a protein capsid. Several models have been proposed for the three-dimensional geometry of the packaged genome, but very little is known of the signature of the molecular packaging motor. For instance, biophysical experiments show that in some systems, DNA rotates during the packaging reaction, but most current biophysical models fail to incorporate this property. Furthermore, studies including rotation mechanisms have reached contradictory conclusions. In this study, we compare the geometrical signatures imposed by different possible mechanisms for the packaging motors: rotation, revolution, and rotation with revolution. We used a previously proposed kinetic Monte Carlo model of the motor, combined with Brownian dynamics simulations of DNA to simulate deterministic and stochastic motor models. We find that rotation is necessary for the accumulation of DNA writhe and for the chiral organization of the genome. We observe that although in the initial steps of the packaging reaction, the torsional strain of the genome is released by rotation of the molecule, in the later stages, it is released by the accumulation of writhe. We suggest that the molecular motor plays a key role in determining the final structure of the encapsidated genome in bacteriophages.