Researchers reveal structure of protein that repairs damage to cancer cells

Chuan He, assistant professor in chemistry, University of Chicago. Biology and chemistry come together in his laboratory like the tightly wound strands of a DNA molecule. Click here for more information.

A team of University of Chicago scientists has shown how two proteins locate and repair damaged genetic material inside cells.

One protein detects and repairs damage in malignant cells that may result from a certain type of cancer therapy. In a paper published in the April 24 issue of the journal Nature, the team raised the possibility of designing a molecule that could interfere with the repair process, making cancer treatment more effective.

Chuan He, Assistant Professor in Chemistry, led the team. His co-authors included Phoebe Rice, Associate Professor in Biochemistry and Molecular Biology at the University of Chicago, and five researchers from his laboratory: Cai-Guang Yang, Chengqi Yi, Erica Duguid, Christopher Sullivan, and Xing Jian. Their work was supported by the National Institutes of Health, the W.M. Keck Foundation and the Arnold and Mabel Beckman Foundation.

In their Nature paper, the scientists determined, for the first time, the crystal structures (showing the three-dimensional framework of atoms) of two related DNA-repair proteins bound to double-stranded DNA: a bacterial protein called AlkB, and a corresponding human protein, ABH2. Scientists had been seeking the structures of these proteins to better understand how they perform their key roles in repairing DNA.

University of Chicago scientists determined the molecular structures of the bacterial AlkB protein and its corresponding human protein, ABH2, shown here chemically cross-linked with strands of DNA. These proteins repair... Click here for more information.

The bacterial protein can bind to either single- or double-stranded DNA. The strands separate during the replication process, but the bacterial protein avoids the latter. “This is very bizarre, because most other DNA repair proteins prefer double-stranded,” He said. The AlkB protein avoids double-stranded DNA because binding it takes more energy.