The extrusion-capture model for chromosome partitioning in bacteria

Abstract

We have proposed that many bacteria harness the energy produced during DNA polymerization by a replication factory to facilitate chromosome partitioning. As illustrated in this review, a number of proteins and DNA sites, particularly those involved in chromosome organization and compaction, are needed for accurate chromosome partitioning. Partitioning of circular bacterial chromosomes can be considered to occur in several phases. First, newly duplicated origin regions move away from each other and away from the central replisome to opposite halves of the cell where they are then somehow maintained at or near the cell quarters. Second, the bulkof chromosomal DNA, which resides between the origin and terminus, is replicated, refolded, and partitioned. Third, DNA replication terminates, sister chromosomes are decatenated, dimers are resolved to monomers (when necessary), and sister termini move to either side of the division septum. After cell division, the process culminates with the repositioning of the terminus to mid cell. There are many interesting and important questions to be explored in the next few years, including: (1) What DNA sites and proteins are responsible for origin movement and for positioning? (2) Are the sites and proteins used during exponential growth the same as those used during development or entry into stationary phase? (3) How is the terminus region positioned to mid cell after division? (4) What, if any, are the differences in partitioning between bacteria that are (B. subtilis, E. coli) and are not (C. crescentus) capable of multifork replication? (5) Are there differences in chromosome partitioning attributable to differences in the physical shape (e. g., rod vs. sphere of bacteria? Perhaps one of the most elusive and interesting issues concerns the nature of positional information: How do bacteria know where to put things and how do they know where the middle, quarters, and eighths are? One of the interesting features of work in bacteria is the vast evolutionary distances that separate model organisms such as E. coli and B. subtilis. We expect that a number of fundamental mechanisms are conserved over such distances, including the use of replication factories. However, it is equally anticipated that some of the details will be different. At first glance it is not always obvious when a mechanism is fundamental versus when it is more family specific. This can result in radically different models and useful debate. B. subtilis and E. coli represent two families of bacteria that include a number of human pathogens. For example, B. subtilis is a member of the low G + C content family along with Staphylococcus, Streptococcus, Enterococcus, and Clostridia, whereas E. coli, itself a potential pathogen, belongs to the γ-proteobacteria family along with Salmonella and Shigella. Our increasing understanding of chromosome partitioning and the cell cycle as a whole in these bacteria has begun to elucidate both important similarities and differences among eukaryotes. Where we find differences in critical cell cycle mechanism, we also find potential drug targets. It is apparent that many of the proteins and mechanisms that are conserved among bacteria are also conserved between eukaryotes and prokaryotes, for example, SMC and the replication factories. Therefore, studies of these basic processes in bacteria have the potential to provide insights into fundamental mechanisms for maintaining genomic integrity in all organisms.