The study offers a specific mechanism by which cells cope with some of the most destructive carcinogens in the environment, including those in cigarette smoke. Many of these carcinogens preferentially damage DNA at guanine – one of the four bases in DNA – blocking, in some cases, the ability of the guanine to partner with cytosine, which can lead to mistakes during replication.
Aneel Aggarwal, PhD, and Deepak Nair, PhD, of the Department of Physiology and Biophysics at Mount Sinai School of Medicine and their colleagues at University of Texas Medical Branch, Galveston discovered that a protein called Rev1 DNA polymerase itself codes for a cytosine to be placed on the replicating strand. The cytosine is inserted based upon the coding information in Rev1 regardless of whether a guanine or another base is present on the DNA.
"This is the first time we have seen a protein serving as a template for DNA synthesis," said Dr. Aggarwal. "This provides an entirely new mechanism by which cells can replicate through DNA damaged by certain carcinogens. It thus opens a novel area of study with the potential for innovative approaches to prevention and treatment of cancer."
Science