Quantifying quadruplexes

Courtesy of Julian Huppert

The paper:

J.L. Huppert and S. Balasubramanian, "G-quadruplexes in promoters throughout the human genome," Nucleic Acids Res, 35:406–13. (Cited in 56 papers)

The finding:

University of Cambridge computational biologists Julian Huppert and Shankar Balasubramanian scanned the human genome in search of the telltale sequences of guanine-rich, four-stranded structures that regulate gene transcription, called G-quadruplexes. The researchers uncovered G-quadruplexes in about 40% of promoter regions across the genome, with most clustered near transcription start sites.

The impact:

Many important promoters—including ones for cancer genes and vascular growth factors—were known to contain G-quadruplexes, but no one had a clue as to whether they performed a specific function. "So it was very important to demonstrate that this wasn't a fluke," says Laurence Hurley, a medicinal chemist at the University of Arizona in Tucson.

The follow-ups:

Huppert's team found that G-quadruplexes also pop up in RNA regions that control protein translation (Nat Chem Biol, 3:218–21, 2007). Shantanu Chowdhury of the Institute of Genomics and Integrative Biology in Delhi, India, also uncovered these guanine-rich regions in the promoters of rats, mice, and chimpanzees (J Med Chem, 51:5641–49, 2008).

The application:

Hurley started a biotech company called Cylene, which is conducting Phase II trials on a small molecule to target the G-quadruplex in the cancer-promoting gene c-myc.