A turnstile for initiation of DNA replication

The rate of DNA replication is controlled by regulating the frequency of its initiation. Two criteria must be met by a proper initiation control mechanism: all chromosomal origins of replication must be initiated in every cell cycle and, in addition, an initiated origin must not be available for a second round of ini t iat ion until the chromosomes have been segregated and the cell has divided. The regular recurrence of initiation of DNA replication at a given t ime in the cell cycle implicates an oscillatory mechanism in the generation of a signal to trigger initiation. Currently, the oscillatory mechanism in Escherichia coil seems most likely to involve a cyclic variation in the concentrat ion of active DnaA proteinL2. DnaA performs the first biochemical steps of initiation at the chromosomal origin oriC 3. When charged with ATP, DnaA binds to ofiC, separates the two DNA strands and allows entry of the enzymes required for semiconservative DNA replication 4. Regulatory aspects of replication initiation at oriC have recently been reviewedS; this article focuses on new developments in our understanding of the mechanisms responsible for temporarily inactivating a recently initiated origin. !rik Boye