The extrusion-capture model for chromosome partitioning in bacteria.

Successful cellular reproduction requires accurate duplication and partitioning (segregation) of the genome. Failure to correctly partition the sister genomes results in aneuploidy. The consequences of these errors range from loss of normal cellular function (e.g., the loss of normal growth controls in tumor cells) to cell death. In prokaryotes with a single chromosome, partitioning failures are fatal for at least one of the two daughter cells; a so-called anucleate cell forms when one daughter receives no chromosome and the other daughter receives two chromosomes. Several findings in recent years have fundamentally altered our view of chromosome partitioning in prokaryotes (for review, see Gerdes et al. 2000; Gordon and Wright 2000; Hiraga 2000; Moller-Jensen et al. 2000; Donachie 2001; Sawitzke and Austin 2001). The flurry of new observations was ignited by adaptation of cell biological techniques used in eukaryotes (immunofluorescence, GFP, and fluorescent in situ hybridization) for use in prokaryotes (Harry et al. 1995; Pogliano et al. 1995; Webb et al. 1995; Niki and Hiraga 1998). This review focuses on chromosome partitioning in bacteria that have a single circular chromosome, specifically, the gram-positive organism, Bacillus subtilis, and the gramnegative organisms, Escherichia coli and Caulobacter crescentus. In these bacteria, DNA replication initiates once per cell division cycle from a specific chromosomal locus, oriC, and proceeds bidirectionally to terminate in a defined region opposite the origin, terC (Fig. 1). The basic components of the DNA replication machinery are highly conserved in bacteria (Kornberg and Baker 1992); in fact, these basic components are functionally conserved from bacteria to mammals (Baker and Bell 1998). Fundamental differences exist between chromosome partitioning in eukaryotes and prokaryotes. In eukaryotes, chromosomes are duplicated in S phase, and sister chromosomes remain together during G2. Chromosome partitioning occurs during M phase, when sister chromosomes are lined up on a metaphase plate, separated from each other, and finally segregated in opposite directions by the combined action of the microtubular spindle and mitotic motors. In contrast to the temporal separation of chromosome replication and partitioning in eukaryotes, regions of the bacterial chromosome, starting with the origin, appear to be partitioned soon after duplication, whereas the remainder of the chromosome awaits replication (Glaser et al. 1997; Gordon et al. 1997; Lewis and Errington 1997; Lin et al. 1997; Mohl and Gober 1997; Webb et al. 1997, 1998; Niki and Hiraga 1998; Sharpe and Errington 1998; Teleman et al. 1998; Jensen and Shapiro 1999; Niki et al. 2000). Thus, in bacteria, DNA replication, chromosome refolding, and chromosome partitioning are concurrent. Given these differences, it is not surprising that there is no evidence that bacteria contain eukaryotic-like mitotic spindles or mitotic motors. As discussed below, it appears that bacteria with circular chromosomes probably power chromosome partitioning differently from eukaryotes. This may be possible because of the much smaller distances that chromosomes move in bacteria. Many bacteria, including B. subtilis and E. coli, are capable of dividing in one-half to one-third of the time it takes to duplicate the genome. To accomplish this, new rounds of DNA replication are initiated before a previous round is completed, giving the replication cycle a head start on the division cycle. This results in cells with multiple bidirectional DNA replication forks (so-called multifork replication), multiple copies of oriC (2, 4, or 8), but only a single, unduplicated terminus region (Fig. 2). Soon after duplication, sister origins are each partitioned in opposite directions. Thus, during multifork replication, bacteria contain positional information regarding not only the current medial division site, but also the future division planes (the cell quarters and cell eighths). Other bacteria, for exampleC. crescentus, are not known to be capable of multifork replication and do not have more than two copies of the origin per cell. Recent studies have revealed common mechanisms involved in chromosome partitioning, along with differences in some of the details between organisms. This review summarizes the following recent findings that have contributed new insights into the mechanism by which bacteria accomplish accurate chromosome partitioning. First, the bacterial chromosome has a defined orientation within cells, and individual regions move 3Corresponding author. E-MAIL adg@mit.edu; FAX (617) 253-2643. Article and publication are at http://www.genesdev. org/cgi/doi/10.1101/ gad.913301.