First Look: DNA Replication

For the first time ever, scientists have captured a single DNA molecule replicating on video — and it's changing the way we think about the entire process. One of the most surprising findings is how much randomness characterizes the process.

“It's a different way of thinking about replication that raises new questions,” Stephen Kowalczykowski, molecular genetics professor at University of California, Davis, said in a press release. “It's a real paradigm shift, and undermines a great deal of what's in the textbooks.”

The researchers watched replicating DNA from E. coli bacteria. The first step in the process always sees the double helix “unzipping” into two strands — a  “leading strand” and a “lagging strand.” Each of these become a template for a new strand that is made to match it, leaving two complete DNA molecules when the process has reached the end. The researchers wanted to measure how fast the enzyme machinery moving along the different strands in opposite directions worked.

The polymerase on the “leading strand” can easily work at a continuous pace, but the polymerase on the “lagging strand” cannot. Until now, scientists believed that the polymerases on the two strands coordinated their movement somehow to ensure that one didn't get too far ahead of the other. However, this video shows that this isn't the case.

Stop And Go

Instead, the progress of the “lagging strand” polymerase looks a lot like stop and go traffic, stopping unpredictably and starting up again at random speeds that can vary tenfold. What seemed like coordination is really just the average outcome over time of this random process of variable speeds and starting and stopping.

“We've shown that there is no coordination between the strands. They are completely autonomous,” Kowalczykowski said in the press release.

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The researchers also discovered that the DNA molecule makes use of a kind of “dead man's switch” that it requires due to this lack of coordination. The switch kicks in to stop the spiral from unzipping too far and lets the polymerase catch up. This is important because it minimizes mutations, but it also prompts the question: how does the dead man's switch know to kick in if the two strands are working independently?

The research, published in Cell, highlights how the human tendency to impose a vision of order on what is often more chaotic in reality can cause us to arrive at the wrong conclusions. The footage also provides some exciting new avenues for research. And while the blueprint to life on our planet might be less organized than we once thought, there's still enough mystery remaining in the DNA puzzle to make discovering new surprises an almost sure bet.

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