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High fidelity keeps human DNA assembly line humming

ing of NTPs hints at a previously unknown quality control station to maintain accuracy of RNA synthesis. If an NTP doesn't match up properly with DNA, the system stalls ?and even backs up to correct the error.

"We're able to show how an error will be sensed and corrected," Burton said. "The quality control system checks NTP loading several ways. If it doesn't match the criteria, it gets booted out."

In addition to better understanding how errors are prevented, Burton's research team also learned ways errors are corrected during rapid RNA synthesis. To learn about error correction, Burton's team stalled the DNA conveyer belt. They did this using a deadly mushroom toxin, alpha-amanitin.

Alpha-amanitin is the poison of the death cap mushroom, which can be deadly to humans. In 54 A.D., Emperor Tiberius Claudius was fed a death cap mushroom by his wife Agrippina to put her son Nero on the throne of ancient Rome. Alpha-amanitin kills people by stalling movement of the DNA conveyer belt.

Finding evidence of quality control gives some perspective to the elegance of cell creation. Burton said it does not mean mistakes never occur. The assembly line analogy holds up there. The human system has an acceptable level of error required to allow for the speed at which cells must reproduce.

"RNA polymerase is one of nature's great designs," Burton said. RNA polymerases are found in bacteria, yeast, plants and humans. The design has endured because of this fidelity mechanism for RNA synthesis. "This is a tried and true design and our study explains why this is an enduring design."

The paper, "Dynamic Error Correction and Regulation of Downstream Bubble Opening by Human RNA Polymerase II," also is authored by research associates Xue Gong and Chunfen Zhang in Burton's lab and Michael Feig, MSU assistant professor of biochemistry and chemistry.


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Source:Michigan State University


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