Fig. 1.

Higher-order organization of DNA replication. (A) Independent polymerases at a replication fork. DNA strands (parental in black, daughters in green) are antiparallel, so the polymerases (gray) move in opposite directions during replication. (B) The trombone model. The two polymerases at a fork are colocalized, forming a replisome. The lagging-strand template is looped so that both polymerases face in the same direction. (C) The train-on-tracks model. The two replisomes are independent and move apart along the DNA template. (D) The factory model. The two replisomes are colocalized and relatively stationary, forming a factory that reels in parental DNA and extrudes looped nascent chromosomes. (E) A schematic of replisome behavior is shown for the three versions of the factory model. For simplicity, the looped organization of the factory model is omitted. Red squares indicate blocks to replication. In the coupled model as originally proposed, each replisome is always the same distance from oriC, and blocking one causes the other to stall. In the semiindependent model, the forks normally progress at the same rate, but uncoupling occurs if one fork is blocked. In the independent model, the forks may initiate at different times and move at different rates, and blocking one fork does not affect the other.