Initiation of chromosome replication in escherichia coli

Various models for the control of the timing of initiation of chromosome replication in Escherichia coli B r have been analyzed. Control mechanisms which require protein synthesis, rifampicin-sensitive RNA synthesis or a fixed cell size at the moment of initiation are judged to be unlikely. Furthermore, evidence for an involvement of two distinct classes of proteins in the preparation for initiation, distinguishable by the sensitivity of their synthesis to chloramphenicol, was not detected. The timing of initiation seems to be controlled by envelope synthesis, apparently by elongation of the cell envelope between the origins of envelope- bound sister chromosomes. Studies on the effects of chloramphenicol and penicillin on initiation suggest that this elongation process may encompass, but does not require, septum-crosswall formation. As a possible mechanism for the control process, it is proposed that the bacterial chromosome contains a segment involved in initiation of chromosome replication. One end of this segment is attached to the cell envelope and the other end is the locus at which replication is initiated (the chromosomal origin). An envelope-bound replication apparatus is driven along the segment by means of envelope growth between it and the attachment site. When the replication apparatus reaches the origin, chromosome replication initiates. The membrane distance now existing between the attachment site and the replication apparatus could define a membrane region for DNA replication in the cell, approximately equal in length to an Okazaki fragment. After replication begins, the new envelope attachment site and replication apparatus are formed, perhaps through transcription of genes in the initiation segment, and envelope growth begins again between them in preparation for the next initiation. By this means, the timing of initiation is determined by the rate of envelope growth.