Initiation of Chromosomal Replication

Abstract

The complex process of bacterial chromosomal replication can be divided into several stages: initiation, priming of chain starts, chain elongation, and termination. Since much of what is known about the initiation of bacterial chromosomal replication comes from studies of Escherichia coli, this chapter concentrates on initiation in that organism. The roles of the crucial sequence elements in the initiation and regulation of chromosomal replication are discussed in this chapter. DnaA protein, a sequence-specific DNA-binding protein, is responsible for setting in motion the cascade of events for initiating chromosomal replication, including origin recognition, strand opening, and loading of the replicative helicase at the sites of the future bidirectional replication forks. SeqA tetramers must interact properly and form active aggregates for binding to hemimethylated DNA to occur. This SeqA aggregation may be important not only for regulating chromosomal replication, but also for chromosomal segregation. Bypassing the normal, DnaA-dependent initiation of chromosomal replication from oriC via constitutive stable DNA replication relieves the growth arrest of cells lacking sufficient acidic phospholipids. Regulated initiation of chromosomal replication likely involves not only its timing during the cell cycle, but also where it happens within the cell. Recently, significant advances have been made in our knowledge of the initiation of chromosomal replication.