Replication fork pausing and recombination or “gimme a break”
- Rodney Rothstein1,4,
- Bénédicte Michel2, and
- Serge Gangloff3
- 1Department of Genetics & Development, Columbia University, College of Physicians & Surgeons, New York, New York 10032-2704 USA; 2Génétique Microbienne, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas, France; 3Commissariat a l'Energie Atomique (CEA) de Fontenay-aux-Roses, Unité Mixte de Recherche 217 Centre National de la Recherche Scientifique (CNRS)–CEA, 92265 Fontenay-aux-Roses, France
This extract was created in the absence of an abstract.
Orderly replication of DNA is a prerequisite to the faithful segregation of the chromosomes before cell division. These processes occur in an environment where the natural order of events can be perturbed by DNA damage, which may in turn cause the replication fork to stall or even break down. Such events can trigger cellular checkpoints, which allow time for repair of damage before replication resumes. It is interesting that replication pausing can also occur naturally and that pausing and specific pause sites have been conserved throughout evolution in both prokaryotes and eukaryotes. Although it appears that these sites are important for the regulation of replication termination and to prevent collisions between the replication and transcription machinery, there is no definitive evidence as to their precise function. In this review we consider replication pausing in prokaryotes and eukaryotes. We distinguish between replication blocks and pause sites as well as programmed versus accidental pausing. We also discuss how pausing can lead to increased recombination.
Programmed replication pauses
Natural pause sites in bacteria
The bidirectional replication of the Escherichia colichromosome starts at the origin (at 84 min) and ends in the diametrically opposed terminus region (Fig. 1). The terminus region is flanked by specific nucleotide sequences, theTer sites, that are bound by the protein Tus (for review, seeHill 1996). The Ter–Tus complex blocks the progression of replication forks in a polar manner by inhibiting the unwinding action of replicative helicases (Sahoo et al. 1995). The complex forms a replication fork trap in which the forks can enter but from which they cannot exit. Although they are called terminators, fork movement beyond these sites can be detected under certain circumstances, suggesting that they are not an absolute barrier to replication and rather act as pause sites. Three of the six Ter sites are located between 23 and 28 …
