Compaction-mediated segregation of partly replicated bacterial chromosome

Bacterial chromosome segregation, ensuring equal distribution of replicated DNA, is crucial for cell division. During fast growth, replication and segregation co-occur. Overlapping cycles of DNA replication and segregation require efficient segregation of the origin of replication (Ori), which is known to be orchestrated by the protein families SMC and ParAB. We used data-driven physical modeling to study the roles of these proteins in Ori segregation. Developing a polymer model of the Bacillus subtilis genome based on Hi-C data, we analyzed chromosome structures in wild-type cells and mutants lacking SMC or ParAB. Wild-type chromosomes showed clear Ori segregation, while the mutants lacked faithful segregation. The model suggests that the dual role of ParB proteins, loading SMCs near the Ori and interacting with ParA, is crucial for Ori segregation. ParB-loaded SMCs compact individual Ori and introduce an effective inter-sister repulsion that regulates the ParAB-activity to avoid the detrimental scenario of pulling both Ori to the same pole. The model makes testable predictions for sister-chromosome-resolved Hi-C experiments and proposes that replicated sister chromosomes segregate via mechanistic cooperation of SMC and ParAB activity.