Three dimensional DNA structure during replication

Prokaryotic chromosomes are circular and typically have one origin of replication. The whole replication process continues in both directions away from the origin until the whole chromosome has been replicated (Figure 10A). The intermediate structures formed by the replication of a circular chromosome are sometimes called theta structures, since they look like the Greek letter theta θ. An animation of the process can be seen in Figure 10B and online at Wikimedia Commons.

Bacterial chromosomes are replicated bidirectionally from the origin of replication, forming structures that look like the Greek letter theta.
Figure 10 Bacterial chromosomes are replicated from a single origin of replication. A (left). Stepped image showing the replication of a circular chromosome, as the replication bubble expands from the origin. The parent strands are shown in black, and the daughter strands are shown in red. Image source: AS CC 4.0 BY SA. B (right). Animated gif showing the synthesis of daughter strands and the separation of the parent strands. The two original strands separate from each other and serve as templates for the synthesis of new strands. Replication is terminated when the forks meet and the two chromosomes separate. Each new identical DNA molecule contains one template strand from the original molecule, shown as a solid line, and one new strand, shown as a dotted line.

In this description and in the figures, we’ve presented this as if the leading strand is synthesized first and the lagging strand second. Even the names give this impression! But the synthesis of leading and lagging strands happens simultaneously. This requires the proteins involved in this process to work in concert. While the leading strand polymerase acts continuously on the leading strand template, the lagging strand polymerase dissociates after each Okazaki fragment, rebinding to each new primer. Throughout this process, the two polymerases stay linked so that as the replication fork moves away from the origin, both strands are replicated at once. To accomplish this, all of the replication participants must be organized very specifically in three dimensional space.

A diagram of the trombone model of replication. The leading strand is on top of the image. The lagging strand is on the bottom. The lagging strand loops around to that synthesis is moving in the same direction in space, although synthesis proceeding away from the replication fork.
Figure 11 Trombone model of replication. In this image, the replication fork is moving toward the right. The lagging and leading strand polymerases move together, linked as part of the replisome. The lagging strand template is looped out and around, allowing the lagging polymerase to move in the same direction as the leading polymerase. The loop gets bigger as more parent DNA is unwound and the lagging polymerase extends an Okazaki fragment. The loop is released when one Okazaki fragment is completed, and a new loop forms when synthesis of a new fragment is begun.

As the replication fork opens, the lagging strand template becomes looped around, as shown in Figure 11, where the lagging strand has been folded under itself to bring the two polymerases closer together. This is called the trombone model of replication because as the fork progresses away from the origin, this loop appears to grow and shrink as the DNA template moves in relation to the polymerase. The entire process is shown in this animation of the replication process, produced by HHMI Biointeractive.

Note: Although they are not shown in the figures of this text, additional subunits of the replisome also participate in the replication process. Additional components of the replication machinery help perform functions like loading and unloading the clamp for new Okazaki fragments and keeping the leading and lagging polymerases together so that both template strands are replicated in concert.

A tangled spring toy
Figure 12 A tangled spring toy.

The three-dimensional structure of the replisome and the length of the DNA strands also cause certain difficulties. Have you ever tried to untangle a spring toy (Figure 12), comb through long tangled hair, or wrestle with the power cord on a hand-held appliance? Just like those examples, the parent and daughter DNA strands become twisted around one another in a way that makes it difficult to both melt the template DNA and separate the two daughter duplexes after replication is complete.

A class of enzymes called topoisomerases relieve the torsional strain caused by melting the double helix and untangle the daughter DNA.


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