Figure 1. Change in size and chromosome content of an Escherichia coli cell with growth rate. Imagine a newborn cell of minimal size (0.5 initiation mass (M_i)) with a single unreplicated chromosome, as might be found in a stationary-phase culture (generation time, ). The diagram illustrates what would happen if such a cell were placed in a relatively poor medium, in which the cell can double its mass every hour (mass doubling time = 60 min), or a very rich medium in which the cell can double in mass every 20 min ( = 20 min). Cells increase in mass exponentially. Chromosomes are represented as circles. In poor medium, growth begins immediately but chromosome replication does not start until cell mass reaches M_i (after 60 min). Replication takes a further 40 min (C period). Septation takes a further 20 min (D period) and the cell divides into two equal sister cells, each with one chromosome, at 120 min. The size of each newborn sister cell is now equal to M_i and chromosome replication can begin again. While the cells continue to grow at this rate ( = 60 min) this process will repeat every 60 min, with newborn cells always equal to 1 M_i. In the rich medium, the cell reaches M_i after 20 min and chromosome replication begins. This round of replication also takes 40 min, followed by 20 min to complete the septum and divide; however, because the cell is growing so quickly it will have reached a mass equivalent to 8 M_i: each sister cell will be 4 M_i. The faster they grow, the larger they will be. Each time M_i doubles, a new round of replication begins, even though the previous one has not yet been completed. After the first 80 min in the rich medium, cells therefore initiate chromosome replication and divide every 20 min, but each newborn cell will have two half-replicated copies of the chromosome. Therefore the faster the cells grow, the more chromosome copies they will have (Cooper and Helmstetter, 1968).

Figure 2. Chromosomal locations of cell cycle genes of Escherichia coli. The chromosome is shown as a circle (4 639 221 base pairs in circumference) with the approximate locations of the cell cycle genes referred to in the text. Each box represents an operon but only the cell cycle-specific genes are shown: the locations of other, noncell cycle-specific genes in these operons are shown by horizontal lines.

Figure 3. Cell division and DNA replication cycle of Escherichia coli. Successive stages (10-min intervals) in cell growth at 37°C in a synthetic medium, which allows cells to double in mass every 80 min. In such a slow growing cell it is possible to see successive stages separated in time, rather than overlapping as they do during rapid growth (in media allowing generation times of less than 60 min at 37°C). The left-hand column shows the continuous (exponential) growth of the rod-shaped cell. The cell envelope consists of three main layers: the outer membrane (faint dotted), the peptidoglycan sacculus (thick grey), and the cell membrane (thin grey). During the early stages of growth, most of the proteins that will eventually be required for cell division are either randomly distributed throughout the cytoplasm (e.g. FtsZ, FtsA: represented as black dots) or, in the case of proteins with membrane domains (e.g. FtsL, FtsI, FtsW, FtsQ, FtsN, FtsK), randomly distributed along the cell membrane. The exceptions are the Min proteins. MinE protein forms a circumferential ring around the cell membrane at the cell centre (thin black ellipse) very early in the cycle. MinC and MinD proteins together coat the inside of the cell membrane in only one half of the cell (heavy black line) but every 2 min they disassemble and move to coat the other half of the cell. Late in the growth of the cell (60 min) all the cytoplasmic and membrane proteins required for cell division also assemble into rings in the cell centre (heavy black ellipse). The rapid movement back and forth of the MinC and MinD proteins seems to prevent the premature assembly of this ring in inappropriate places, while the presence of the MinE ring seems to block the action of these inhibitors at the cell centre and so allow the cell division ring to form there. During the next 20 min this ring contracts, apparently pulling in the cell membrane, while at the same time the sacculus grows inward, as a double layer following the contracting cell membrane (70 min). It currently seems probable that FtsZ and FtsA form the contractile ring, connected to the cell membrane by ZipA, while FtsI and perhaps FtsW synthesize the ingrowing septum. Most of the remaining proteins may coordinate the contraction of the cell membrane and the synthesis of the septum. FtsK may play a special role in the final closure of the septum and the formation of the new cell poles (ends). During this process the outer membrane also invaginates as the two layers of the septum split apart, perhaps because another protein, Lpp, links this membrane to the sacculus. The formation of the cytokinetic ring and the start of cell division normally take place immediately after the attainment of a critical cell length (equal to two unit cell lengths: 2L_u²) and the completion of chromosome replication – two separate processes that normally coincide in time. The E. coli chromosome consists of a single covalently closed circle of double helical DNA. Although some 1000 times greater in circumference than the length of the cell itself, the single chromosome is folded and packed into the cell to form a diffuse mass: the nucleoid (shown as a grey body within the cell). Recent cytological studies have shown that this DNA is not randomly folded because, in young cells, one locus (oriC, the site at which chromosome replication begins; ‘o’) is located near one end of the cell, while the region opposite on the circle (ter, the site at which chromosome replication terminates; ‘t’) is located near the opposite pole. The stages of chromosome replication are shown on the right. The DNA is shown as an open circle (at approximately 1/1000 of the scale of the cells on the left). When the cell reaches a critical mass (initiation mass: (M_i)) chromosome replication begins. The initial events in replication are the separation of the complementary DNA strands at oriC, carried out by the ATP-bound form of DnaA protein, followed by the entry of the proteins of the replication complex (‘replisome’) and synthesis of new complementary DNA strands. DNA synthesis is confined to a location in the cell centre, where the old chromosome is fed progressively into the replication complex and newly replicated parts are extruded. Premature reinitiation of replication at the two newly completed copies of oriC is prevented by SeqA protein. Soon after replication begins, the two new copies of the oriC region rapidly move to opposite ends of the cell; unreplicated DNA remains near the cell centre. Completion of chromosome replication and subsequent packaging of the two sister chromosomes into the two new cells requires a further series of events. The two replisomes meet and complete replication in the ter region, but, because a circular double helix has been replicated, the two completed circles of DNA are interlinked (concatenated) at the completion of replication. Decatenation, the unlinking of the circles, requires double-strand breakage and rejoining and is carried out by a specific topoisomerase, Topo IV (the product of the parC and parE genes). A further process is required in some cells: if recombination has taken place between replicated parts of the chromosome, the final result of complete replication is a single double-sized circle, a chromosome dimer. Resolution of such dimers into two sister monomers takes place by site-specific recombination at a special site (dif) located in the ter region. Resolution requires specific resolvases (XerC and XerD proteins) but also needs the FtsK protein, which is also located at the cell centre as part of the cytokinetic ring of proteins. Finally, the MukB protein may compact the nucleoids, so that the two sister chromosomes contract away from the septum, each out of harm's way within the appropriate new cell compartment. And round again, for about 3.7 × 10⁹ years, so far.