Chromosome segregation in a minimal bacterial cell driven by SMC protein complexes.

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.