IBI-5 Seminar: DNA-polymer topology orchestrates the segregation and spatial organization of bacterial chromosomes during replication
Dmitry Fedosov
Apratim Chatterji
Indian Institute of Science Education and Research, IISER-Pune, India
Join us in person in Building 04.16, Room 2001
Abstract:
The mechanism and driving forces of chromosome segregation in the bacterial cell cycle of E. coli is one of the least understood events in its life cycle. Using principles of entropic repulsion between DNA-polymer loops confined in a cylinder, we use Monte Carlo simulations to show that the segregation is spontaneously enhanced by the adoption of a certain DNA-polymer architecture as replication progresses. Secondly, the chosen polymer-topology ensures its self-organization along the cell axis while segregation is in progress, such that various chromosomal segments (loci) get spatially localized as seen in-vivo.
The evolution of loci positions match the corresponding experimentally reported results for E.coli using FISH. Additionally, the contact map generated using our bead-spring model reproduces the four macro-domains of the experimental Hi-C maps. We modify the architecture by adding just four crosslinks at specific positions along the chain contour in 500 monomer bead-spring ring polymer, which represents the chromosome. After replication of our model-polymer, we obtain two 500-monomer ring polymers, which spontaneously get segregated and organized by virtue of their polymer topology.
Thus we have proposed a framework which reconciles many spatial organizational aspects of E. coli chromosome as seen in-vivo, and provides a consistent mechanistic understanding of the process underlying segregation. Certain proteins are expected to contribute to change the DNA-polymer architecture. We also observe quantitative match of FISH data and HiC data for another bacteria C.crescentus where we use another polymer topology. We have extended our studies to investigate chromosome organization in fast growth conditions for E.coli.