The naturally occurring antibiotic Actinomycin D (ActD) was approved by the Food and Drug Administration as a chemotherapy drug in 1964 and has been widely used for nearly 50 years to treat a variety of tumor types. Since then, scientists have discovered that ActD works by blocking DNA transcription, the process that transcribes DNA into RNA, a macromolecule that codes for the proteins necessary for cell survival.

Inhibition by ActD is a good thing in rapidly dividing and transcribing cancer cells, but healthy cells are also susceptible to ActD, which makes it toxic, like many forms of chemotherapy.

Despite its long history, the molecular details of ActD’s function remained a mystery — until now.

“If you don’t know how it works, then you can’t design a new molecule that has the same characteristics [but less toxicity],” said Mark Williams, a physics professor in the College of Science at Northeastern University. “This is why we decided to study it.”

Williams and his experimental biophysics team used “optical tweezers” to probe the molecule and its interaction with DNA to determine the underlying mechanism by which ActD prevents transcription.

The findings were published on Feb. 10 in the journal Nucleic Acids Research.

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