Scientists at the Georgia Institute of Technology have made an important step toward solving a critical puzzle relating to a chemical reaction that leads to DNA mutation, which underlies many forms of cancer. The research, which uncovers knowledge that could be critical to the development of strategies for cancer prevention and treatment, appears in the August 2006 edition (Volume 128, issue 33) of the Journal of the American Chemical Society.
The process that gives rise to mutations in DNA, or mutagenesis, is a complex one involving a series of chemical reactions, which are not completely understood. A free radical, a stable neutral atom or a chemical group containing at least one unpaired electron, can scavenge an electron from DNA in a process known as oxidation, creating a hole in place of the scavenged electron. Such oxidation events can be caused by natural processes occurring in the body, or by ionizing radiation. It's well known that the ionization hole can travel long distances of up to 20 nanometers along the base pairs that form the rungs of the DNA ladder (discussed by Landman, Schuster and their collaborators in a 2001 Science article, volume 294, page 567). It is also well known that the hole tends to settle longer at spots in the DNA where two guanines (G) are located next to each other.
It's the next step that has eluded DNA researchers for decades - somehow the hole in the ionized DNA reacts with water. This critical step is the first in a series that brings about a change in the DNA molecule one that evades the body's proof reading mechanism and leaves the altered DNA coding for the wrong proteins. When the wrong proteins are produced, it can lead through a complicated chain of events to an abnormally high rate of cell division the result is cancer.
"We set out to explore the elementary processes that lead to mutagenesis and eventually cancer," said Uzi Landman, director of the Center for Computational Materia
Contact: David Terraso
Georgia Institute of Technology