Our chromosomes are much longer than the space in which they are packaged in the cell. Chromosome compaction is on the order of several thousand fold, yet these chromosomes have to be unraveled every cell cycle to be replicated accurately and the daughter chromosomes must be topologically unlinked to allow their separation and segregation into the daughter cells. Management of chromosome shape and topology in bacteria falls to three groups of proteins: the DNA topoisomerases, the structural maintenance of chromosome proteins (SMC), and the small double-strand DNA-binding nucleoid-associated proteins.
Accurate transmission of the genetic information requires complete duplication of the chromosomal DNA each cell division cycle. However, the idea that replication forks would form at origins of DNA replication and proceed without impairment to copy the chromosomes has proven naive. It is now clear that replication forks stall frequently as a result of encounters between the replication machinery and template damage, slow-moving or paused transcription complexes, unrelieved positive superhelical tension, covalent protein-DNA complexes, and as a result of cellular stress responses. These stalled forks are a major source of genome instability.