Novel mechanism for DNA replication discovered

Mount Sinai School of Medicine researchers first to discover that a protein can provide the coding information for DNA replication

Since the discovery of the structure of DNA by James Watson and Francis Crick in 1953, the paradigm for DNA replication has stated that the DNA itself codes for the appropriate pairings for replication. In other words, if a guanine base is on the original strand of DNA then its partner, a cytosine base, will pair to it on the replicated strand. In a study published in this week’s issue of Science, researchers from Mount Sinai School of Medicine report on the first instance in which a protein, rather than the DNA, provides the coding information.

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.”