Limiting DNA replication to once and only once

In Escherichia coil cells, the origin of chromosomal replication is tempora rily inactivated after initiation has occurred. Origin sequestration is the first line of defence against over-initiation, providing a time window dur ing which the initiation potential can be reduced by: (i) titration of DnaA proteins to newly replicated chromosomal elements; (ii) regulation of the activity of the DnaA initiator protein; and (iii) sequestration of the dnaA gene promoter. This review represents the first attempt to consider togeth er older and more recent data on such inactivation mechanisms in order to a nalyze their contributions to the overall tight replication control observe d in vivo. All cells have developed mechanisms for origin inactivation, but those of other bacteria and eukaryotic cells are clearly distinct from tho se of E. coli. Possible differences and similarities are discussed.