Mao Closing In On Answers

According to the American Cancer Society, there will be an estimated 1,688,780 NEW Cancer Cases diagnosed and 600,920 cancer-related deaths in in the U.S. 2018

These numbers are stark and sobering. Worse yet, we still don’t know exactly why cancer develops in its victims or how to stop it.

A publication in Nature Nanotechnology by Kent State University researchers and their colleagues at Kyoto University in Japan, however, may offer new understanding about what turns good cells bad.

Hanbin Mao, Professor of Chemistry and Biochemistry, co-authored a paper with his graduate students, Prakash Shrestha and Sagun Jonchhe, along with Kyoto University colleagues, “Confined space facilitates G-quadruplex formation,” published in March 2017.

Hanbin Mau

The article discusses the genetic factors that influence formation of cancer cells. “Traditionally, DNA has a two-strand shape — the double helix — and its purpose is to code the proteins that form life,” Mao said. “But recently, people have discovered that some DNA has four strands and we call this the G-Quadruplex. This is associated with the inhibition of cancer cells.”

However, while most G-Quadruplex DNA is beneficial, Mao said some strands go bad and such mutations actually will enable cancer cell growth. To understand why this happens, scientists first had to learn why DNA sometimes develops into four-strand structures.

All DNA is generated by enzymes and operates like an assembly line. However, Mao said, there comes a point where DNA makes a decision to form a double helix or a quadruplex. He said most DNA takes the two-strand route simply because it is the easiest path.

Mao said nanometer- sized spaces inside the enzymes are where these formations occur, but the inability to mimic these spaces in laboratory settings has prohibited deeper study of the G-Quadruplex formation. That is, until now.

With help from chemists and engineers at Kyoto University, Mao and graduate students Prakash Shrestha and Sagun Jonchhe used “DNA origami” to create a “nano cage.” They accomplished this through single-molecule mechanochemical sensing — a technology Mao’s lab developed in 2014. Over the past few years, he has published several studies involving the use of “laser tweezers,” a tool that provides the ability to hold extraordinarily small micrometer- and nanometer-sized biological materials in place.

That technology allowed Mao to create 6X6 nanometer-sized cages, then observe how DNA folded into different shapes inside the space.

“It’s easier for the DNA to fold inside the cage,” he said. “It folds to adapt to the small space, and here DNA naturally folds into the G-Quadruplex.”

He said the process occurs two to three orders of magnitude faster inside the cage than outside, folding 100,000 times per second — a speed that makes forming G-Quadruplex as fast and easy as forming a double helix.

“We may now be able to follow the fate of the cell to be cancerous or healthy,” he said. “So we can perhaps learn how to introduce molecules or chemicals to interfere with that process.”

He said scientists can use ligands — bonded molecules — to facilitate this effect with greater potency, thereby reducing the likelihood that cancer cells will form.

“We can prevent or better treat cancer by stabilizing G-Quadruplex structures,” Mao said.

POSTED: Wednesday, April 11, 2018 - 1:29pm
UPDATED: Friday, May 11, 2018 - 10:00am