Rare ‘DNA and RNA jitters’ may explain random mutations

Published 2015-03-13 20:28. Updated 2015-03-13 20:40

In a new study being published in Nature, researchers present a possible explanation to how seemingly random errors are made in the molecular machinery that copies DNA and produces proteins in a living cell. In a flicker of a second, DNA or RNA bases sometimes make the slightest change to mimic a different base. These rare ‘jitters’ seems to appear at about the same frequency as the DNA copying machinery makes mistakes or the ribosome incorporates new amino acids, which might make them the basis of random changes that drive evolution and diseases like cancer.

The molecular process to copy DNA in a living cell is amazingly fast and accurate when it comes to pairing up the correct bases – G with C and A with T – into each new double helix. The ribosome is a high-throughput machinery producing proteins based on a RNA triple matching. These machineries work by recognizing the shape of the right base pair combinations, and discarding those that do not fit together correctly.

Yet for approximately every 10,000 to 100,000 bases copied, a mistake is made that if uncorrected will be immortalized in the genome as a mutation. For decades, researchers have wondered how these seemingly random errors are made.

Sophisticated technique

By using a sophisticated technique called NMR relaxation dispersion, a team of researchers from Duke University and Karolinska Institutet could witness DNA bases making the slightest of changes – shifting a single atom from one spot to another or simply getting rid of it altogether – to temporarily mimic the shape of a different base. These ‘quantum jitters’ are exceedingly rare and only flicker into existence for a thousandth of a second, and also appears at about the same frequency that the DNA copying machinery makes mistakes or the ribosome adds the wrong amino acid.

According to the researchers, it seems like structure of DNA is inherently tailored to allow mistakes to happen at a certain level. Without these errors life would not have evolved. On the other hand, with too many jitters our genes would mutate out of control. 

Participating in this study from Karolinska Institutet did Dr. Katja Petzold, Principal investigator at the Department of Medical Biochemistry and Biophysics. Study leader has been Dr. Hashim Al-Hashimi from Duke University. The investigation was funded by an NIH grant and an Agilent Thought Leader Award. This news article is partly a rewrite from a press release issued by Duke University.

Publication

Visualizing transient Watson–Crick-like mispairs in DNA and RNA duplexes
Isaac J. Kimsey, Katja Petzold, Bharathwaj Sathyamoorthy, and Hashim M. Al-Hashimi
Nature, online 11 March 2015, doi:10.1038/nature14227

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