New tool to help unravel the function of an elusive DNA structure

A Rensselaer researcher has developed a new tool to help unravel the function of an elusive DNA structure. The findings, which were presented today at the 230th national meeting of the American Chemical Society (ACS) in Washington, D.C., could lead to a better understanding of diseases such as cancer and diabetes.

The standard version of the human genome is a double-stranded helix of complementary bases: adenine binds to thymine and cytosine binds to guanine. "Our focus is on a different type of DNA structure, the 'G-quartet,' that arises from hydrogen bonds between guanines only," says Linda McGown, professor and chair of the Department of Chemistry and Chemical Biology at Rensselaer Polytechnic Institute.

Scientists have long speculated about the existence of these G-quartets, as well as the role they might play in the human body, but direct evidence has remained elusive. To help answer these questions, McGown and her students at Rensselaer and Duke University have been examining this unusual structure, which is a rectangular array of four guanines, each hydrogen-bonded to its two nearest neighbors.

McGown has developed a "directed proteomic" strategy to compare G-quartet protein-binding profiles in different populations of cells. "This is essentially a fishing experiment using hooks comprised of G-quartet-forming sequences from the DNA genome, in hopes of catching proteins that might bind to such structures in the human nucleus," she says. McGown recently discovered that insulin binds to a G-quartet formed by a sequence that occurs in the insulin promoter gene.

"The possibility that insulin may participate in its own regulation is intriguing, and adds to the growing evidence relating G-quartet formation and diabetes," she says. She plans to apply her technique to G-quartet-forming sequences that occur in other regions of human chromosomes and have been implicated in cancer, aging, and genetic diseases. Her goal is to increase understanding of the role of G-quartets in health and disease, leading to the identification of new biomarkers and medical therapies.

McGown is one of 18 Rensselaer researchers presenting at the ACS meeting in Washington, along with Rensselaer President Shirley Ann Jackson, who will be speaking at a special event celebrating the 10th anniversary of the ACS Scholars Program. Her talk will focus on the urgent need to build the next generation of scientists, which she asserts requires fostering a national plan and a national will to succeed.