After Meselson and Stahl’s work was published, investigators confirmed that other organisms also use semiconservative replication. No evidence was found for conservative or dispersive replication. There are, however, several different ways in which semiconservative replication can take place, differing principally in the nature of the template DNA—whether it is linear or circular.

A segment of DNA that undergoes replication is called a replicon; each replicon contains an origin of replication. Replication starts at the origin and continues until the entire replicon has been replicated. Bacterial chromosomes have a single origin of replication, whereas eukaryotic chromosomes contain many.

A common type of replication that takes place in circular DNA, such as that found in E. coli and other bacteria, is called theta replication (Figure 9.4) because it generates a structure that resembles the Greek letter theta (θ). In Figure 9.4 and all subsequent figures in this chapter, the original (template) strand of DNA is shown in gray and the newly synthesized strand of DNA is shown in red.

In theta replication, double-stranded DNA begins to unwind at the origin of replication, producing single nucleotide strands that then serve as templates on which new DNA can be synthesized. The unwinding of the double helix generates a loop, termed a replication bubble. Unwinding occurs at one or both ends of the bubble, making it progressively larger. DNA replication on both of the template strands is simultaneous with unwinding. The point of unwinding, where the two single strands separate from the double-stranded DNA helix, is called a replication fork.

If there are two replication forks, one at each end of the replication bubble, the forks proceed outward in both directions in a process called bidirectional replication, simultaneously unwinding and replicating the DNA until they eventually meet. If a single replication fork is present, it proceeds around the entire circle to produce two complete circular DNA molecules, each consisting of one old and one new nucleotide strand.

Circular DNA molecules that undergo theta replication have a single origin of replication. Because of the limited size of these DNA molecules, replication starting from one origin can traverse the entire chromosome in a reasonable amount of time. The large linear chromosomes in eukaryotic cells, however, contain far too much DNA to be replicated speedily from a single origin. The replication of eukaryotic chromosomes is initiated at thousands of origins.

Typical eukaryotic replicons are from 20,000 to 300,000 base pairs in length. At each origin of replication, the DNA unwinds and produces a replication bubble. Replication takes place on both strands at each end of the bubble, with the two replication forks spreading outward. Eventually, the replication forks of adjacent replicons run into each other, and the replicons fuse to form long stretches of newly synthesized DNA (Figure 9.5). The replication and fusion of all the replicons lead to two identical DNA molecules. Important features of theta replication and linear eukaryotic replication are summarized in Table 9.1. TRY PROBLEM 19