Skip to main content

Michelle Wang, Tung T. Le, & Meiling Wu publish findings in Nature Chemical Biology on how a chemotherapeutic agent works to inhibit cancer

Graphic showing stretching assay - experimental confirguration for stretching DNA under a constant velocity

The image contains a key: a black dot represents ATP, a yellow star represents etoposide, and a red line drawing that looks similar to a vertebrae represents topo II.

A gray rectangle runs along the bottom of the image. It is slanted to the left. An arrow on the left of the rectangle, pointing to the left, is labeled "constant velocity." Sitting on top of the gray rectangle on the right side is a pink rectangle with curved left and right sides, so it has an hourglass shape. This pink shape is labeled "optical trap."

A gray circle with a long black line (like a tail) stretching down and to the left is overlapping with the optical trap on the trap's center left side. This represents a double-stranded DNA molecule anchored to the optically trapped microsphere.

To the left of the optical trap and around the tail of the double-stranded DNA molecule, ATP dots, etoposide stars, and topo II drawings are scattered around the area.

Exciting results from the lab of Michelle Wang!

David Nutt's Cornell Chronicle article "Tweezers untangle chemotherapeutic’s impact on DNA" describes how research findings published by the Michelle Wang Lab group, including co-lead authors and HHMI-funded researchers Tung T. Le and Meiling Wu, "provid[e] a fresh view into the ways a common chemotherapy agent, etoposide, stalls and poisons the essential enzymes that allow cancer cells to flourish."

Le et al. discovered that etoposide, a chemotherapeutic poison of topoisomerase II (topo II), promotes topo II to compact DNA, trap DNA loops, and pause DNA supercoiling relaxation, thus converting topo II into a strong roadblock to DNA processing. In the Nature Chemical Biology research briefing, Dr. Le and Dr. Wang explain the significance of this work, noting that it "demonstrates that single-molecule experiments can be a valuable, but often overlooked, addition to studies affecting human health. We anticipate that the techniques used here will be beneficial in studying a broad range of topoisomerase inhibitors and poisons, serving as sensitive screening tools for defining drug mechanisms and enzyme isoform specificity, and providing valuable insights for end-user treatments."

Find the full paper "Etoposide promotes DNA loop trapping and barrier formation by topoisomerase II" at Nature Chemical Biology.