Loop Extruders can maintain bacterial chromosome organization in E. coli

Abstract

DNA in all living organisms, including bacteria, must be compactly folded to fit within the confines of the cell. In bacteria like E. coli, the DNA is organized into a single, circular chromosome, which, if fully extended, would measure about 1000 times the length of the cell. Thus, chromosomal compaction and the chromosomes spatial organization within the nucleoid are crucial for various cellular functions. Experiments suggest that E. coli maintains its chromosomal organization through internal structural properties. One of the crucial mechanisms to maintain a stable organization are so called Structural Maintenance of Chromosomes protein complexes (SMC), which extrude the genomic material into loops and thereby, compact and organize the chromosome. However, it is yet unclear how exactly loop extruders contribute to the chromosomal organization and whether loop extruders alone could be sufficient to maintain stable organization.

To answer this question, we developed the model of an Asymmetrically Looped Ring Polymer and show theoretically and through simulations that randomly loaded loop extruders can maintain a stable Left-ori-Right organization in E. coli-like chromosomes. We theoretically explore how stochastic dynamics of loop extruders on a polymer affect the polymers physical characteristics. Our simulations exhibit the enhancement of the L-o-R organization with increasing loop size and the failing of a stable organization in symmetrically structured configurations of the chromosome. Additionally, we find that the stochastic fluctuations induced by the loop extruders dynamic might lead to flipping between energetically favorable configurations. Thus, our model enables us to explain the macroscopic organizational stability of an Asymmetrically Looped Ring Polymer through the microscopic mechanism of loop extruders.