Determining the replication factory settings

Saner et al. describe how neighboring DNA regions stochastically assemble into replication factories in budding yeast.

A replicon is a stretch of DNA duplicated from a single replication origin. In eukaryotes, multiple replicons assemble into sub-nuclear structures called replication factories, where the replicons are duplicated by DNA polymerases and other replication proteins. Replication factories help to coordinate efficient DNA synthesis, but how replicons are organized into these structures is unclear.

Saner et al. used live-cell imaging to follow the replication of different replicons along a budding yeast chromosome. Surprisingly, whether the replicons duplicated in the same or different replication factories varied from cell to cell. Neighboring replicons were more likely to duplicate in the same factory than replicons spaced further apart. Once assembled into the same factory, however, replicons remained associated for several minutes, long enough, perhaps, for replication to be completed.

Using super-resolution microscopy, Saner et al. found that many replication factories contain only a single replicon and that few factories contain more than four. Mathematical models of factory assembly supported the idea that neighboring replicons randomly associate to form factories of variable size and composition. Senior author Tomoyuki Tanaka is now interested in determining whether similar principles apply to the formation of replication factories in mammalian nuclei and to the assembly of other sub-nuclear structures involved in transcription and DNA repair.