Study reveals secrets of DNA mutation

"They're bad guys, but they pretend to be good guys to survive," researcher Zucai Suo said.

By Brooks Hays

Feb. 1 (UPI) -- According to new research, some mutational DNA bases are able to avoid detection by the body's natural defense systems and incorporate themselves into the human genome.

The DNA base pair formed by guanine and thymine, a mutational mismatch, are able to shape-shift so they blend in with the rest of the DNA ladder, or helix.


"When these two bases form a hydrogen bond by accident, at first, they don't fit quite right," Zucai Suo, professor of chemistry and biochemistry at Ohio State University, said in a news release. "They stick out along the DNA helix, so normally it's easy for the enzymes that replicate DNA to detect them and fix them."

And normally, they do get caught and the mismatch is rectified. But sometimes, the base pair can change shapes before detection, avoiding the attention of genetic repair mechanisms.

"They're bad guys, but they pretend to be good guys to survive," Suo said.

This common form of DNA mutation is responsible for disease, the aging process and the experimental adaptations that drive evolution.

All genetic coding is formed by four bases: adenine, thymine, cytosine and guanine -- or A, T, C and G. All healthy base pairs are either A-T or C-G. Any combination besides A-T and C-G is considered a mutation.


G-T is the most common mutation found in human DNA. A G-T mutation occurs once for every 10,000 to 100,000 base pairs. There are 3 million base pairs in the human genome. So every genome has anywhere from 30,000 to 300,000 G-T mutations.

To better understand how G-T pairs form and disguise themselves, Suo and doctoral student Walter Zahurancik inserted the duo into a DNA strand using a DNA-replicating enzyme. The researchers froze the chemical reactions driving the mutation process at different time intervals to study the details of the mutational mechanism.

They found the enzyme can efficiently pair the two bases, but they form an odd-shaped molecule. However, in just a fraction of a second, the bases can rearrange themselves and successfully snap into play in the DNA helix.

A-T and C-G base pairs fit because they're shaped in ways that compliment one another. When they pair, they're very energy efficient. Mutational pairings are not and must alter themselves to overcome this energy barrier.

That's what happens when G-T pairs form -- they become just efficient enough to pass muster and avoid detection.

Scientists believe their findings -- detailed this week in the journal Nature -- can help researchers better understand the factors that cause DNA mutations.


"An interesting question is: What determines the mutation rate in a living organism," said Duke University researcher Hashim M. Al-Hashimi. "From there, we can begin to understand the specific conditions or environmental stressors that can elevate errors."

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