Abstract
Chromosome replication is a fundamental process in all domains of life. To accurately transmit genetic material to offspring, the initiation of chromosome replication is tightly regulated to ensure that it occurs only once in each cell division cycle. In the model bacterium Caulobacter crescentus, the CtrA response regulator inhibits the origin of replication at the pre-replication stage. Inactivation of CtrA permits the universal DnaA initiator to form an initiation complex at the origin, leading to replication initiation. Subsequently, the initiation complex is inactivated to prevent extra initiation. Whereas DNA replication occurs periodically in exponentially growing cells, replication initiation is blocked under various stress conditions to halt cell cycle progression until the normal condition is restored or the cells adapt to the stress. Thus, regulating the initiation complex plays an important role in not only driving cell cycle progression, but also maintaining cell integrity under stress. Multiple regulatory signaling pathways controlling CtrA and DnaA have been identified and recent studies have advanced our knowledge of the underlying mechanistic and molecular processes. This review focuses on how bacterial cells control replication initiation, highlighting the latest findings that have emerged from studies in C. crescentus.
Highlights
As an aquatic, gram-negative alphaproteobacterium, Caulobacter crescentus is a prime model organism to study the dynamics of bacterial chromosomal replication (Batut et al, 2004; Curtis and Brun, 2010; Tsokos and Laub, 2012; Hallez et al, 2017; Surovtsev and JacobsWagner, 2018)
Regulatory components that coordinate the activities of DnaA and CtrA during the cell cycle play a fundamental role in determining whether Cori initiates replication, which ensures cell integrity in C. crescentus (Fig. 3–5)
Because cyclic di-GMP levels oscillate throughout the cell cycle (Fig. 5A), the increased levels that occur during the G1-to-S phase transition permit timely induction of cycle kinase A (CckA) phosphatase activity, leading to inactivation of CtrA and subsequent initiation of chromosome replication
Summary
To accurately transmit genetic material to offspring, the initiation of chromosome replication is tightly regulated to ensure that it occurs only once in each cell division cycle. In the model bacterium Caulobacter crescentus, the CtrA response regulator inhibits the origin of replication at the pre-replication stage. Inactivation of CtrA permits the universal DnaA initiator to form an initiation complex at the origin, leading to replication initiation. Regulating the initiation complex plays an important role in driving cell cycle progression, and maintaining cell integrity under stress. Multiple regulatory signaling pathways controlling CtrA and DnaA have been identified and recent studies have advanced our knowledge of the underlying mechanistic and molecular processes. This review focuses on how bacterial cells control replication initiation, highlighting the latest findings that have emerged from studies in C. crescentus
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