FALL 2006
“Pinball Protons” Can Lead to DNA Damage
by Phillip Lee Williams

Call it a “Pinball Proton.” Computational chemists at the University of Georgia have discovered that when a proton is knocked off one of the pairs of bases that make up DNA, a chain of damage begins that can eventually lead to serious disorders such as cancer.

Doctoral student Maria Lind and Henry F. Schaefer III, Graham Perdue Professor of Chemistry, led the research, published in May in the journal Proceedings of the National Academy of Sciences. Other authors on the paper are doctoral student Partha Bera, postdoctoral associate Nancy Richardson and recent doctoral graduate Steven Wheeler.

The report is the first to describe how protons, which can be knocked away by radiation or chemical exposure, can cause “lesions” in DNA. “This kind of damage in DNA subunits is about as basic as you can get,” Schaefer said. “This is the simplest kind of lesion possible for such a system.”

The double-helix structure of DNA has been known for more than half a century. This basic building block of life can “unzip” itself to create copies, a process at the heart of cell replication and growth. DNA is made of four bases, Adenine, Guanine, Thymine and Cytosine, and each one pairs with its opposite to form bonds where the information of life is stored. Thus, Guanine pairs with Cytosine, and Adenine with Thymine.

The UGA team studied how the removal of a proton from the Guanine-Cytosine (G-C) base pair created lesions that can lead to replication errors. The lesions are breaks in the hydrogen bonds, of which there are two in the G-C base pair. A base pair lacking a proton may either change its bonding angle or break entirely – both of which cause improper replication.

“The C-G subunit is usually totally planar [flat],” Lind said. “If it twists, it could simply pull apart. This new study is the first evidence that protons may influence cancer cell formation.”

For more information, contact Henry Schaefer at