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Abstract Minimal bacterial cells such as JCVI‐Syn3A provide a powerful system for uncovering the essential mechanisms of chromosome organization and segregation. Lacking canonical systems such as Min and ParABS, JCVI‐Syn3A relies primarily on structural maintenance of chromosomes (SMC) protein complexes for partitioning. Here, we investigate a four‐dimensional (4D; three spatial dimensions plus time) polymer‐based model of the JCVI‐Syn3A chromosome (543 kbp) that captures replication and partitioning dynamics across the full cell cycle. Our simulations reproduce chromosome segregation mediated by SMC‐driven loop extrusion and reveal how segregation depends on the number of SMC complexes, their translocation speed, and their dwell time on DNA. A systematic parameter scan shows that segregation is strongly predicted by the effective loop coverage, which represents the expected fraction of the chromosome extruded into loops. We generate contact maps for stationary‐phase cells to directly connect our simulations with 3C experiments, and for replicating chromosomes throughout the cell cycle to provide new, testable predictions for synchronized cell populations. Our results suggest that SMC protein complexes and topoisomerases can drive chromosome segregation in minimal cells without additional partitioning systems provided loop extrusion achieves sufficient genomic coverage.
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Dynamics of chromosome organization in a minimal bacterial cell
Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculatein silicochromosome contact maps that capture inter-daughter interactions. Finally, we present a methodology to map the polymer model of the chromosome to a Martini coarse-grained representation to prepare molecular dynamics models of entire Syn3A cells, which serves as an ultimate means of validation for cell states predicted by the WCM.
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- PAR ID:
- 10469522
- Publisher / Repository:
- Frontiers Media
- Date Published:
- Journal Name:
- Frontiers in Cell and Developmental Biology
- Volume:
- 11
- ISSN:
- 2296-634X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.3389/fcell.2023.1214962
