ParA and its functions that go beyond chromosome segregation in Caulobacter crescentus

Maintaining the integrity of the chromosome after the completion of each cell cycle is paramount for bacterial survival. Mechanistic details remain incomplete for how bacteria manage to retain intact chromosomes in each daughter cell after each cell division. In this study, we examined the partitioning protein ParA and its functions on chromosomal maintenance that go beyond triggering the onset of chromosome segregation. Our data demonstrate that ParA can promote the onset of chromosome replication initiation in Caulobacter crescentus cells with sub-physiological levels of the replication initiator protein DnaA. Increasing the cellular levels of ParA results in over-initiation of chromosome replication in this bacterium. We show that the ability of ParA to impact replication initiation is independent from ParAs ability to trigger the onset of chromosome segregation. Surprisingly, our work revealed that perturbing the balance of the components of ParAs nucleotide-dependent cycle can have severe defects in cell cycle coordination and can potentially be lethal to the cell. Increasing the levels of different forms of ParA also impacted cell length independent of their replication initiation frequencies. Our results, together with past observations, suggest a model where ParA can serve as a checkpoint coordinating various cell cycle events involved in maintenance of the chromosome.