Researchers at the University of California, Davis, have just reported a small but significant accomplishment: catching the replication of a single DNA molecule on video for the first time. And the footage has revealed some surprising details about this structure on which all life depends.
DNA is composed of two strands bound together in a helical shape, like a twisting ladder. These strands are made of four bases—adenine, guanine, cytosine and thymine, abbreviated as A, G, C and T, respectively—strung together in various patterns and paired in specific ways across the rungs of the ladders. A always pairs with T, and C always pairs with G. Sugar and phosphate molecules help provide architectural support to the ladder-like structure. Human DNA contains about 3 billion bases. Discrete, repeated sequences of bases form the individual genes that encode the instructions for all our working parts. And every time a cell divides, which happens incredibly often, DNA replicates so that each new cell contains a complete copy of our entire genome, or genetic blueprint.
The process of DNA replication is a tremendous source of wonder and focus for research. The helix must unwind and have each strand copied smoothly and quickly. An enzyme called helicase triggers the unwinding and another called primase initiates the replication process. A third, called polymerase, travels the length of a strand, adding the requisite base pairs along the way, leaving behind a new strand. Imagine splitting a ladder down the middle and assembling matching halves so that where there was once one ladder now there are two. That is DNA replication, only in place of saws, nails, wood and glue, there are enzymes and many microscopic and complex processes. Mysteries abound when it comes to this hereditary material.
To better probe those mysteries, geneticist and microbiologist Stephen Kowalcyzkowski and colleagues watched DNA from bacteria replicate. They wanted to see exactly how fast the enzymes worked on each strand.
This first-ever view, shown in the video above, revealed a surprise: replication stopped unpredictably and moved at a varying pace. "The speed can vary about 10-fold," Kowalczykowski said in a statement. The two strands also replicated at different speeds. Sometimes the copying stalled on one strand while proceeding on the other. "We've shown that there is no coordination between the strands," said Kowalczykowski. "They are completely autonomous." The process, the researchers report in their study, published in Cell, is much more random than previously suspected.
The three enzymes—helicase, primase and polymerase—are also not alwys in sync. Even if polymerase stops its replication work, helicase can keep unzipping the helix. That lack of coordination leaves the half-helix of DNA exposed and vulnerable to damage. Such exposure is known to trigger repair mechanisms within the cell. Errors in replicating DNA, while often corrected, can also result in genetic abnormalities that in turn lead to diseases.
This new look at DNA transforms the scientific understanding about replication. "It's a real paradigm shift," said Kowalcyzkowski, "and undermines a great deal of what's in the textbooks."
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